Phenome-wide Association Analysis of Substance Use Disorders in a Deeply Phenotyped Sample.

BACKGROUND: Substance use disorders (SUDs) are associated with a variety of co-occurring psychiatric disorders and other SUDs, which partly reflects genetic pleiotropy. Polygenic risk scores (PRSs) and phenome-wide association studies are useful in evaluating pleiotropic effects. However, the comparatively low prevalence of SUDs in population samples and the lack of detailed information available in electronic health records limit these data sets' informativeness for such analyses. METHODS: We used the deeply phenotyped Yale-Penn sample (n = 10,610 with genetic data; 46.3% African ancestry, 53.7% European ancestry) to examine pleiotropy for 4 major substance-related traits: alcohol use disorder, opioid use disorder, smoking initiation, and lifetime cannabis use. The sample includes both affected and control subjects interviewed using the Semi-Structured Assessment for Drug Dependence and Alcoholism, a comprehensive psychiatric interview. RESULTS: In African ancestry individuals, PRS for alcohol use disorder, and in European individuals, PRS for alcohol use disorder, opioid use disorder, and smoking initiation were associated with their respective primary DSM diagnoses. These PRSs were also associated with additional phenotypes involving the same substance. Phenome-wide association study analyses of PRS in European individuals identified associations across multiple phenotypic domains, including phenotypes not commonly assessed in phenome-wide association study analyses, such as family environment and early childhood experiences. CONCLUSIONS: Smaller, deeply phenotyped samples can complement large biobank genetic studies with limited phenotyping by providing greater phenotypic granularity. These efforts allow associations to be identified between specific features of disorders and genetic liability for SUDs, which help to inform our understanding of the pleiotropic pathways underlying them.

Home-Based Primary Care: Beyond Extension of the Independence at Home Demonstration.

The Independence at Home (IAH) Demonstration Year 2 results confirmed that the first-year savings were 10 times as great as those of the pioneer accountable care organizations during their initial 2 years. We update projected savings from nationwide conversion of the IAH demonstration, incorporating Year 2 results and improving attribution of IAH-qualified (IAH-Q) Medicare beneficiaries to home-based primary care (HBPC) practices. Applying IAH qualifying criteria to beneficiaries in the Medicare 5% claims file, the effect of expanding HBPC to the 2.4 million IAH-Q beneficiaries is projected using various growth rates. Total 10-year system-wide savings (accounting for IAH implementation but before excluding shared savings) range from $2.6 billion to $27.8 billion, depending on how many beneficiaries receive HBPC on conversion to a Medicare benefit, mix of clinical practice success, and growth rate of IAH practices. Net projected savings to the Centers for Medicare and Medicaid Services (CMS) after routine billing for IAH services and distribution of shared savings ranges from $1.8 billion to $10.9 billion. If aligning IAH with other advanced alternative payment models achieved at least 35% penetration of the eligible population in 10 years, CMS savings would exceed savings with the current IAH design and HBPC growth rate. If the demonstration were simply extended 2 years with a beneficiary cap of 50,000 instead of 15,000 (as currently proposed), CMS would save an additional $46 million. The recent extension of IAH, a promising person-centered CMS program for managing medically complex and frail elderly adults, offers the chance to evaluate modifications to promote more rapid HBPC growth.

Spatial and temporal drivers of avian population dynamics across the annual cycle.

Untangling the spatial and temporal processes that influence population dynamics of migratory species is challenging, because changes in abundance are shaped by variation in vital rates across heterogeneous habitats and throughout the annual cycle. We developed a full-annual-cycle, integrated, population model and used demographic data collected between 2011 and 2014 in southern Indiana and Belize to estimate stage-specific vital rates of a declining migratory songbird, the Wood Thrush (Hylocichla mustelina). Our primary objective was to understand how spatial and temporal variation in demography contributes to local and regional population growth. Our full-annual-cycle model allowed us to estimate (1) age-specific, seasonal survival probabilities, including latent survival during both spring and autumn migration, and (2) how the relative contribution of vital rates to population growth differed among habitats. Wood Thrushes in our study populations experienced the lowest apparent survival rates during migration and apparent survival was lower during spring migration than during fall migration. Both mortality and high dispersal likely contributed to low apparent survival during spring migration. Population growth in high-quality habitat was most sensitive to variation in fecundity and apparent survival of juveniles during spring migration, whereas population growth in low-quality sites was most sensitive to adult apparent breeding-season survival. These results elucidate how full-annual-cycle vital rates, particularly apparent survival during migration, interact with spatial variation in habitat quality to influence population dynamics in migratory species.

Demographic trends among older cannabis users in the United States, 2006-13.

BACKGROUND AND AIMS: The ageing US population is providing an unprecedented population of older adults who use recreational drugs. We aimed to estimate the trends in the prevalence of past-year use of cannabis, describe the patterns and attitudes and determine correlates of cannabis use by adults age 50 years and older. DESIGN: Secondary analysis of the National Survey on Drug Use and Health survey from 2006 to 2013, a cross-sectional survey given to a nationally representative probability sample of populations living in US households. SETTING: USA. PARTICIPANTS: A total of 47 140 survey respondents aged ≥ 50 years. MEASURES: Estimates and trends of past-year use of cannabis. FINDINGS: The prevalence of past-year cannabis use among adults aged ≥ 50 increased significantly from 2006/07 to 2012/13, with a 57.8% relative increase for adults aged 50-64 (linear trend P < 0.001) and a 250% relative increase for those aged ≥ 65 (linear trend P = 0.002). When combining data from 2006 to 2013, 6.9% of older cannabis users met criteria for cannabis abuse or dependence, and the majority of the sample reported perceiving no risk or slight risk associated with monthly cannabis use (85.3%) or weekly use (79%). Past-year users were more likely to be younger, male, non-Hispanic, not have multiple chronic conditions and use tobacco, alcohol or other drugs compared with non-past-year cannabis users. CONCLUSIONS: The prevalence of cannabis use has increased significantly in recent years among US adults aged ≥ 50 years.

Seasonal change in tropical habitat quality and body condition for a declining migratory songbird.

Many migratory songbirds spend their non-breeding season in tropical humid forests, where climate change is predicted to increase the severity and frequency of droughts and decrease rainfall. For conservation of these songbirds, it is critical to understand how resources during the non-breeding season are affected by seasonal patterns of drying, and thereby predict potential long-term effects of climate change. We studied habitat quality for a declining tropical forest-dwelling songbird, the wood thrush (Hylocichla mustelina), and tested the hypothesis that habitat moisture and arthropod abundance are drivers of body condition during the overwintering period. We examined habitat moisture, abundance of arthropods and fruit, and condition of individual birds (n = 418) in three habitat types--mature forest, mature forest with increased presence of human activity, and riparian scrub--from October to April. We found a strong pattern of habitat drying from October (wet season) to March (prior to spring migration) in all habitats, with concurrent declines in arthropod and fruit abundance. Body condition of birds also declined (estimated ~5 % decline over the wintering period), with no significant difference by habitat. Relatively poor condition (low body condition index, low fat and pectoral muscles scores) was equally apparent in all habitat types in March. Climate change is predicted to increase the severity of dry seasons in Central America, and our results suggest that this could negatively affect the condition of individual wood thrushes.