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Objectives: Alcohol use disorder (AUD) is a global health problem with significant negative consequences, including preventable deaths. Although olfactory dysfunction is associated with chronic alcohol drinking, the relationship among specific types of olfactory deficits, depressive symptoms, and problematic drinking remains to be explored. Here, we examined the prevalence of olfactory distortion (parosmia) and hallucination (phantosmia) and assessed their associations with problematic drinking and depressive symptoms., Methods: In April-June 2022, 250 participants across the spectrum of AUD were recruited for assessment in the National Institute on Alcohol Abuse and Alcoholism COVID-19 Pandemic Impact on Alcohol study. Surveys covered self-reported olfactory function, depressive symptoms, and problematic drinking, with key measures assessed, including the Alcohol Use Disorders Identification Test and the Patient Health Questionnaire. Predictors in the analysis included parosmia and phantosmia, with covariates comprising age, sex, socioeconomic status, race, ethnicity, COVID-19 infection status, and smoking status., Results: Among 250 individuals, 5.2% experienced parosmia and 4.4% reported phantosmia. Parosmia was associated with higher Alcohol Use Disorders Identification Test scores (β = 7.14; 95% confidence interval = 3.31, 10.96; P < 0.001), whereas phantosmia was linked to higher Patient Health Questionnaire scores (β = 3.32; 95% confidence interval = 0.22, 6.42; P = 0.03). These associations persisted in both the full sample and the subset of participants without COVID-19., Conclusions: Our study highlights strong existing links among olfactory deficits, problem drinking, and depressive symptoms, underscoring the need to assess smell impairments in clinical settings. Future research should explore these connections further to develop new treatments for individuals with AUD and depression., Competing Interests: The authors report no conflicts of interest., (Copyright © 2024 Written work prepared by employees of the Federal Government as part of their official duties is, under the U.S. Copyright Act, a “work of the United States Government” for which copyright protection under Title 17 of the United States Code is not available. As such, copyright does not extend to the contributions of employees of the Federal Government.)

Introduction: Previous observational studies assessing β2-agonist/-antagonist use on PD risk have yielded conflicting results. We evaluated the relationship between β2-agonist use and the incidence of Parkinson's disease in patients with chronic lung disease., Methods: We performed a retrospective cohort analysis on a 20% random sample abstracted from a traditional (fee-for-service) Medicare program in the United States. Inclusion criteria were individuals over 65 years old diagnosed with asthma, COPD, and/or bronchiectasis who were enrolled in a prescription drug (standalone Part D) plan over 2007-2010 and alive through 2014. The main outcome measure was a diagnosis of Parkinson's disease over the period 2011-2014, in relation to the number of 30-day-equivalent drug claims over 2007-2010. Logistic regression analysis was performed on a sample including 236,201 Medicare beneficiaries., Results: The sample was 68% female, 80% white, and on average 77 years old as of 2010. Compared to non-users, β2-agonist users were more likely to be younger (76.3y versus 78.0y), smokers (40.4% versus 31.1%) and asthmatic (62.4% versus 28.3%). The odds ratio for a β2-agonist claim on PD development was 0.986 (95% CI 0.977-0.995) after adjusting for demographics, smoking history, respiratory exacerbations, comorbidities, and other drug use. Risk reductions were larger for males than females (0.974 versus 0.994, P = 0.032), and for individuals with COPD compared to those with asthma (0.968 versus 0.998, P = 0.049). Reverse causality was addressed with a Cox analysis that allowed β2-agonist use to vary from medication initiation to disease onset. By the end of the follow-up period, β2-agonist use was shown to be associated with a true protective effect against PD onset., Discussion: β2-agonist use is associated with decreased risk of PD incidence. Further investigation, possibly including clinical trials, is warranted to strengthen the evidence base supporting clinical decision-makers looking to repurpose pharmaceuticals to prevent neurodegenerative disease onset., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: During the past three years, Dana Goldman (DG) has received research support, speaker fees, travel assistance, or consulting income from the following sources: Amgen, Blue Cross Blue Shield of Arizona, Bristol Myers Squibb, Cedars-Sinai Health System, Edwards Lifesciences, Gates Ventures, Genentech, Gilead Sciences, Johnson & Johnson, Kaiser Family Foundation, National Institutes of Health, Novartis, Pfizer, Roche, and Walgreens Boots Alliance. DG holds equity in EntityRisk. DG reports personal fees from Biogen and GRAIL as a scientific advisor. Until November 2019, DG served on the Scientific Advisory Board of ACADIA Pharmaceuticals. Until March 2020, DG served as a scientific advisor to Precision Medicine Group. This does not alter our adherence to PLOS ONE policies on sharing data and materials., (Copyright: © 2022 Nadeem et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Objectives: To determine the use of formulary restrictions (prior authorization and step therapy) on the use of non-vitamin K antagonist oral anticoagulants (NOACs) and their effect on health outcomes., Study Design: Longitudinal cohort study. We identified a sample of Medicare beneficiaries with an incident diagnosis of atrial fibrillation (AF) in 2011 to 2015 and followed them until the end of 2016 or death. We compared anticoagulant use and health outcomes associated with Medicare Part D plan coverage of NOACs., Methods: The primary outcomes were composite rates of death, stroke, transient ischemic attack, and systemic embolism. We used Cox proportional hazards models to estimate the association between formulary restrictions and adverse health outcomes., Results: Beneficiaries enrolled in Part D plans that restricted access to NOACs had a lower probability of NOAC use (30.2% vs 32.2%), worse adherence conditional on NOAC use (32.1% vs 34.3% adherent), and longer delays in filling an initial prescription (46% vs 55% filled within 30 days of AF diagnosis). Beneficiaries in restricted plans had higher aggregate risk of mortality/stroke/transient ischemic attack (adjusted HR, 1.098; 95% CI, 1.079-1.118)., Conclusions: Limiting access to NOACs may exacerbate current underuse of anticoagulants and increase the risk of stroke among patients with newly diagnosed AF. Pharmacy benefit managers and Part D plans need to continuously review the appropriateness of formulary policies to ensure patient access to effective medications.

Abstract: This multiagency report developed by the Interagency Collaboration for Genomics for Food and Feed Safety provides an overview of the use of and transition to whole genome sequencing (WGS) technology for detection and characterization of pathogens transmitted commonly by food and for identification of their sources. We describe foodborne pathogen analysis, investigation, and harmonization efforts among the following federal agencies: National Institutes of Health; Department of Health and Human Services, Centers for Disease Control and Prevention (CDC) and U.S. Food and Drug Administration (FDA); and the U.S. Department of Agriculture, Food Safety and Inspection Service, Agricultural Research Service, and Animal and Plant Health Inspection Service. We describe single nucleotide polymorphism, core-genome, and whole genome multilocus sequence typing data analysis methods as used in the PulseNet (CDC) and GenomeTrakr (FDA) networks, underscoring the complementary nature of the results for linking genetically related foodborne pathogens during outbreak investigations while allowing flexibility to meet the specific needs of Interagency Collaboration partners. We highlight how we apply WGS to pathogen characterization (virulence and antimicrobial resistance profiles) and source attribution efforts and increase transparency by making the sequences and other data publicly available through the National Center for Biotechnology Information. We also highlight the impact of current trends in the use of culture-independent diagnostic tests for human diagnostic testing on analytical approaches related to food safety and what is next for the use of WGS in the area of food safety., (Published 2022 by the International Association for Food Protection. Not subject to U.S. Copyright.)

Given that New York State's (NYS) was the first epicenter of the COVID-19 pandemic in the United States (US), we were interested in potential racial/ethnic differences in pregnancy-related experiences among women pregnant during versus prior to the pandemic. We surveyed 1,525 women (18-44 years) proportionate to geographic and sociodemographic distribution between June 9, 20 and July 21, 20. We carried out bivariate analysis of various social and pregnancy-related factors by racial/ethnic identity (White, Black, Hispanic) and binary logistic and linear regression assessing the association between race/ethnicity, pregnancy prior to/during the pandemic, demographic characteristics, health and social wellbeing, and employment as an essential worker with pregnancy-related healthcare delays and changes. Overall, Black and Hispanic women were significantly more likely to experience a host of negative prenatal and postpartum experiences. In general, multivariate analyses revealed that individuals who were pregnant during the pandemic, lived in NYC, participated in social welfare programs, lacked health insurance, and/or were essential workers were more likely to report delays in prenatal and postpartum care and/or more changes/negative experiences. In light of previous evidence of racial disparities in birth experiences, the higher rates of negative pregnancy/birth-care and postpartum/newborn-care experiences among Black and Hispanic women in bivariate analysis warrant further inspection given that their aggregation for multivariate analysis may have obscured differences at the level of individual events. Findings support continued efforts for universal health insurance and improved social welfare programs. Guidelines are needed to protect essential workers' access to health services, particularly related to pregnancy given the time-sensitive nature of this care.Supplemental data for this article is available online at https://doi.org/10.1080/08964289.2021.1997893 .

The aging process in OECD countries calls for a better understanding of the future disease prevalence, life expectancy (LE) and patterns of inequalities in health outcomes. In this paper we present the results obtained from several dynamic microsimulation models of the Future Elderly Model family for 12 OECD countries, with the aim of reproducing for the first time comparable long-term projections in individual health status across OECD countries. We provide projections of LE and prevalence of major chronic conditions and disabilities, overall, by gender and by education. We find that the prevalence of main chronic conditions in Europe is catching-up with the United States and significant heterogeneity in the evolution of gender and educational gradients. Our findings represent a contribution to support policymakers in designing and implementing effective interventions in the healthcare sector., (© 2021 John Wiley & Sons Ltd.)

Continuing education directed at building providers' skills and knowledge in geriatrics represents a practical approach to addressing the geriatric mental health (MH) care workforce shortage. To inform the development of professional training curricula, we surveyed MH providers (N = 65) at a Veterans Affairs medical center on working with older persons with dementia (PwD) and informal caregivers. Providers rated service provision to PwD and caregivers as highly important but endorsed modest self-efficacy. Half of respondents were minimally confident in managing risk of harm to self or others in a PwD. Respondents believed PwD can benefit from MH treatments, yet identified several barriers to providing care, including inadequate time and staffing resources. Interest in geriatric training topics was high. Findings demonstrate that MH providers at this site value care provision to PwD and caregivers, and desire additional training to serve this population. System-level barriers to MH care for PwD should also be identified and addressed.

Alzheimer's disease (AD) is the predominant cause of dementia and a leading cause of death globally. With no cure or treatment to slow disease progression, AD-related healthcare costs are substantial and increase as the severity of the disease progresses. Given the complexity of this disease, including initial pathophysiological damage occurring decades before clinical manifestation, finding new impactful treatments for AD relies on highly innovative research and development. However, such sizable and sustained investments bring into question whether conventional value assessment models are fit for this purpose. In this article, we examine the importance and challenges of assimilating the perspectives of varied stakeholders, including patients, caregivers, health systems, payers, and society at large, into a comprehensive value assessment model that may be well suited for a breakthrough treatment for AD.

Objectives: We determined the temporal association between clinical and serological disease manifestations and development of cutaneous small vessel vasculitis in a large prospective multiethnic cohort., Methods: Patients with SLE diagnosed according to the Systemic Lupus International Collaborating Clinics (SLICC) classification criteria or the revised classification criteria as defined by the American College of Rheumatology (ACR) were enrolled in the Hopkins Lupus Cohort. Cutaneous small vessel vasculitis was determined as a component of the Systemic Lupus Erythematosus Disease Activity Index. SLE-associated cutaneous small vessel vasculitis lesions were reported clinically. They presented as punctate lesions, palpable purpura, tender erythematous plaques or macules with or without necrosis. No histopathological diagnosis was pursued to confirm the diagnosis of vasculitis or to differentiate it from other causes of digital lesions in patients with SLE. Disease manifestations that preceded the first occurrence of cutaneous small vessel vasculitis lesions were analysed using Kaplan-Meier. Cox regression analysis was used to assess the relationship between baseline clinical and immunological manifestations and the development of cutaneous small vessel vasculitis. We adjusted for gender, race and age at SLE diagnosis., Results: A total of 2580 patients were studied: 52.4% were Caucasian and 39.4% were African-American. The mean age of the cohort was 45.5±14.5 years. The mean years of cohort follow-up was 7.9±7.6. Cutaneous small vessel vasculitis was observed in 449 (17.3%). The mean time to cutaneous vasculitis after SLE diagnosis was 4.78 years (95% CI 3.96 to 5.60). At least 159 (35%) patients had recurrences of cutaneous vasculitis lesions. Discoid rash, Raynaud's phenomenon, myositis, anaemia, Coombs' positivity, leucopenia, anti-Smith and anti-RNP (Ribonucleoprotein) were significantly associated with the development of cutaneous vasculitis. The SLICC/ACR Damage Index score was higher in patients with cutaneous vasculitis compared with those without cutaneous vasculitis., Conclusions: Cutaneous vasculitis is frequent (17.3%) and often recurrent (35%). African-Americans are at higher risk of developing cutaneous small vessel vasculitis than Caucasians. Clinical presentations such as myositis and haematological manifestations are predictors of cutaneous vasculitis development. The presence of cutaneous vasculitis is associated with increased organ damage., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

The objective of this study was to examine the association between surgeon characteristics, procedural volume, and short-term outcomes of hemodialysis vascular access. A retrospective cohort study was performed using Medicare Part A and B data from 2007 through 2014 merged with American Medical Association Physician Masterfile surgeon data. A total of 29,034 procedures met the inclusion criteria: 22,541 (78%) arteriovenous fistula (AVF) and 6,493 (22%) arteriovenous graft (AVG). Of these, 13,110 (45.2%) were performed by vascular surgeons, 9,398 (32.3%) by general surgeons, 2,313 (8%) by thoracic surgeons, 1,517 (5.2%) by other specialties, and 2,696 (9.3%) were unknown. Every 10-year increase in years in practice was associated with a 6.9 per cent decrease in the odds of creating AVF versus AVG ( P = 0.02). Surgeon characteristics were not associated with the likelihood of vascular access failure. Every 10-procedure increase in cumulative procedure volume was associated with a 5 per cent decrease in the odds of vascular access failure ( P = 0.007). There was no association of provider characteristics or procedure volume with survival free of repeat AVF/AVG or TC placement at 12 months. A significant portion of the variability in likelihood of creating AVF versus AVG is attributable to the provider-level variation. Increase in procedure volume is associated with decreased odds of vascular access failure.

Objectives: To measure value in the delivery of inpatient care and to quantify its variation across U.S. regions., Data Sources / Study Setting: A random (20%) sample of 33,713 elderly fee-for-service Medicare beneficiaries treated in 2,232 hospitals for a heart attack in 2013., Study Design: We estimate a production function for inpatient care, defining output as stays with favorable patient outcomes in terms of survival and readmission. The regression model includes hospital inputs measured by treatment costs, as well as patient characteristics. Region-level effects in the production function are used to estimate the productivity and value of the care delivered by hospitals within regions., Data Collection / Extraction Methods: Medicare claims and enrollment files, linked to the Dartmouth Atlas of Health Care and Inpatient Prospective Payment System Impact Files., Principal Findings: Hospitals in the hospital referral region at the 90th percentile of the value distribution delivered 54% more high-quality stays than hospitals at the 10th percentile could have delivered, after adjusting for treatment costs and patient severity., Conclusions: Variation in the delivery of high-value inpatient care points to opportunities for better quality and lower costs., Competing Interests: The authors have declared that no competing interests exist.

Purpose: The purpose of this study is to compare the motivations of interventional radiology (IR) residency, IR fellowship, and diagnostic radiology (DR) applicants., Materials and Methods: A questionnaire was distributed to IR integrated residency and IR fellowship applicants for the 2018 National Resident Matching Program (NRMP) Match. Survey respondents scored the influence of 13 aspects of IR on their career decision. These results were combined with a previously published survey of DR residency applicants from 2016 who were asked the same questions. Pairwise comparisons to survey responses were made between IR residency and IR fellowship as well as IR residency and DR residency respondents., Results: There were 202 of 657 DR residency respondents (response rate 30.7%), 114 of 295 IR residency respondents (response rate 38.6%), and 70 of 169 IR fellowship respondents (response rate 41.4%). Compared with DR respondents, IR residency respondents rated the following factors more positively: influence of a mentor (P = .030), perceived job satisfaction (P < .001), job market (P < .001), salary (P < .001), intellectual stimulation (P = .030), the use of emerging or advanced technology (P < .001), and the visual nature of the field (P < .001). In contrast, DR residency respondents rated flexible work hours (P < .001), physics (P < .001), and competitiveness of the application process (P < .001) more positively than IR respondents. Compared with IR fellowship respondents, IR residency respondents rated flexible work hours (P = .002), the job market (P = .020), physics (P < .001), and salary (P < .001) more positively, and competitiveness (P = .002) was felt to be more negative for residency applicants., Conclusion: The motivations for pursuing IR residency differ from both DR residency and IR fellowship. Understanding these motivations can help to recruit top quality IR residency applicants., (Copyright © 2018 American College of Radiology. Published by Elsevier Inc. All rights reserved.)

Objective: To examine the impact of Medicaid prior authorization for atypical antipsychotics on the prevalence of schizophrenia among the prison population. Study, Design: We collected drug-level information on prior authorization restrictions from Medicaid programs in 30 states to determine which states had prior authorization requirements before 2004. We linked the regulatory data to a survey of prison inmates conducted in 2004., Methods: We used a sample of 16,844 inmates from a nationally representative survey and analyzed the data using cross-sectional regression. To capture the impact of prior authorization, we estimated 2 models: the first included an indicator variable for states requiring prior authorization, and a second model used per capita atypical usage., Results: Evidence indicated that prior authorization restrictions on atypical antipsychotics are associated with an increase in the odds of a schizophrenic resident being imprisoned in a state. State-level prior authorization requirements for atypical antipsychotics are associated with a 2.7% increase in the likelihood that an imprisoned inmate displays psychotic symptoms, and a 1.25 increase in the likelihood that an inmate was previously diagnosed with schizophrenia by a physician. Higher state-level atypical prescriptions per capita are also associated with lower likelihood of psychotic symptoms and of prior schizophrenia diagnosis among prisoners., Conclusions: Prior authorization requirements for atypical antipsychotics, which are designed to reduce healthcare costs, are associated with greater prevalence of mental illness within the criminal justice system.This association raises important questions about whether increased costs to the criminal justice system might mitigate or offset prescription drug savings created by prior authorization requirements.

Purpose: To estimate the employer costs associated with employee obesity., Design: The study used cross-sectional analysis of employee health-risk assessment, disability, workers' compensation, and medical claims data from 2006 to 2008., Setting: The study took place in the United States from 2006 to 2008., Subjects: A panel database with 29,699 employees drawn from a panel of employers and observed for 3 years each (N = 89,097) was used., Measures: Workdays lost owing to illness and disability; the cost of medical, short-term disability, and workers' compensation claims; and employees' adjusted body mass indices (BMI) were measured., Analysis: We model the number and probability of workdays lost from illness, short-term disability, and workers' compensation events; short-term disability and workers' compensation payments; and health care spending as a function of BMI. We estimate spline regression models and fit results using a third-degree fractional polynomial., Results: Probability of disability, workers' compensation claims, and number of days missed owing to any cause increase with BMI above 25, as do total employer costs. The probability of a short-term disability claim increases faster for employees with hypertension, hyperlipidemia, or diabetes. Normal weight employees cost on average $3830 per year in covered medical, sick day, short-term disability, and workers' compensation claims combined; morbidly obese employees cost more than twice that amount, or $8067, in 2011 dollars., Conclusion: Obesity is associated with large employer costs from direct health care and insurance claims and indirect costs from lost productivity owing to workdays lost because of illness and disability.

This paper investigates whether individuals are sufficiently informed to make reasonable choices in the health insurance exchanges established by the Affordable Care Act (ACA). We document knowledge of health reform, health insurance literacy, and expected changes in healthcare using a nationally representative survey of the US population in the 5 wk before the introduction of the exchanges, with special attention to subgroups most likely to be affected by the ACA. Results suggest that a substantial share of the population is unprepared to navigate the new exchanges. One-half of the respondents did not know about the exchanges, and 42% could not correctly describe a deductible. Those earning 100-250% of federal poverty level (FPL) correctly answered, on average, 4 out of 11 questions about health reform and 4.6 out of 7 questions about health insurance. This compares with 6.1 and 5.9 correct answers, respectively, for those in the top income category (400% of FPL or more). Even after controlling for potential confounders, a low-income person is 31% less likely to score above the median on ACA knowledge questions, and 54% less likely to score above the median on health insurance knowledge than a person in the top income category. Uninsured respondents scored lower on health insurance knowledge, but their knowledge of ACA is similar to the overall population. We propose that simplified options, decision aids, and health insurance product design to address the limited understanding of health insurance contracts will be crucial for ACA's success.

Purpose: To develop a risk-scoring tool to identify in a base year patients likely to have high medical spending in the subsequent year and to understand the role obesity and obesity reduction may play in mitigating this risk., Design: Cross-sectional analysis, using commercial claims and health risk assessment data., Setting: United States, 2004-2009., Subjects: Panel of 192,750 person-year observations from 116,868 unique working-age employees of large companies., Measures: Probability of high medical expenses (80th percentile or above) in the following year; adjusted body mass index (BMI)., Analysis: Generate risk scores by modeling the likelihood of high next-year expenses as a function of base-year age, sex, medical utilization, comorbidities, and BMI. Estimate the effect of simulated bariatric intervention on patient risk scores., Results: Individuals with higher BMI were more likely to be categorized in the very high risk group, in which the average annual medical expense was $8621. A weight-loss intervention transitioning a patient to the next lower obesity class was predicted to reduce this risk by 1.5% to 27.4%-comparable to hypothetically curing a patient of depression or type 2 diabetes., Conclusion: A logistic model was used to capture the effect of BMI on the risk of high future medical spending. Weight-loss interventions for obese patients may generate significant savings by reducing this risk.

Objectives: To estimate the frequency and characteristics of opioid prescribing by multiple providers in Medicare and the association with hospital admissions related to opioid use., Design: Retrospective cohort study., Setting: Database of prescription drugs and medical claims in 20% random sample of Medicare beneficiaries in 2010., Participants: 1,808,355 Medicare beneficiaries who filled at least one prescription for an opioid from a pharmacy in 2010., Main Outcome Measures: Proportion of beneficiaries who filled opioid prescriptions from multiple providers; proportion of these prescriptions that were concurrently supplied; adjusted rates of hospital admissions related to opioid use associated with multiple provider prescribing., Results: Among 1,208,100 beneficiaries with an opioid prescription, 418,530 (34.6%) filled prescriptions from two providers, 171,420 (14.2%) from three providers, and 143,344 (11.9%) from four or more providers. Among beneficiaries with four or more opioid providers, 110,671 (77.2%) received concurrent opioid prescriptions from multiple providers, and the dominant provider prescribed less than half of the mean total prescriptions per beneficiary (7.9/15.2 prescriptions). Multiple provider prescribing was highest among beneficiaries who were also prescribed stimulants, non-narcotic analgesics, and central nervous system, neuromuscular, and antineoplastic drugs. Hospital admissions related to opioid use increased with multiple provider prescribing: the annual unadjusted rate of admission was 1.63% (95% confidence interval 1.58 to 1.67%) for beneficiaries with one provider, 2.08% (2.03% to 2.14%) for two providers, 2.87% (2.77% to 2.97%) for three providers, and 4.83% (4.70% to 4.96%) for four or more providers. Results were similar after covariate adjustment., Conclusions: Concurrent opioid prescribing by multiple providers is common in Medicare patients and is associated with higher rates of hospital admission related to opioid use.

Objectives: This study was designed to assess the effect of tyrosine kinase inhibitor (TKI) use on nonpharmaceutical medical spending for patients with chronic myeloid leukemia (CML), and estimate the association between cost-sharing and the TKI medication possession ratio (MPR)., Study Design: The retrospective study covered the 13 years from 1997 to 2009., Methods: Analyses were conducted using a large administrative health insurance claims database covering 45 large employers. From this database, 995 unique patients with CML were identified, with 3,765 patient-years; of these patients, 415 (or 1,689 patientyears) were TKI users. We estimated the association of TKI use with total pharmaceutical spending and total non-pharmaceutical medical spending. In addition, we characterized plan-level cost-sharing rules for TKIs and assessed whether these were associated with the MPR for TKI therapy among CML patients., Results: TKI users averaged $26,406 in annual non-pharmaceutical medical spending, compared with $38,194 for non-users; this was a difference of approximately 30%, which was statistically significant at the 5% level. The median patient out-ofpocket payment was $25, which increased to $63 at the 75th percentile and to $122 at the 95th percentile. MPRs were 94.8 at the median cost-sharing level and 100.0 at the 75th percentile and higher. There was no statistically significant association between cost-sharing and MPR., Conclusions: Use of TKIs was associated with a 30% reduction in non-pharmaceutical medical spending for CML patients. This difference is approximately equal to 40% of the incremental pharmaceutical cost associated with using TKI therapy. The net annual cost of TKI therapy is roughly $15,000. An informal calculation suggests that this is well within the range of conventional cost-effectiveness thresholds. On balance, coverage of TKIs is relatively generous, with the vast majority of patients exhibiting high levels of adherence to therapy.

Objectives: To assess the effects of patient cost sharing on initiation of disease-modifying therapies (DMTs) in multiple sclerosis (MS)., Study Design: Retrospective claims database study of privately insured patients newly diagnosed with MS between 2004 and 2008 from 33 large employers., Methods: We assessed the effects of plan-level cost-sharing on DMT initiation during a 2-year follow-up period after diagnosis. Incident cases were identified by 2 or more claims with ICD-9 codes for MS within a year, subsequent to a year with no such claims. Covariates for adjustment included age, gender, relationship to primary beneficiary, comorbid conditions, and calendar year, as well as unobserved factors that did not vary within plans over time., Results: Out of a sample of 3460 patients meeting criteria for inclusion, only 17% initiated a DMT within 2 years of diagnosis. An increase in the cost-sharing rate from zero to the 95th percentile (17.8%) was predicted to decrease initiation within 2 years of diagnosis by 2.9 percentage points, or 12.7% (P = .019)., Conclusions: High cost-sharing is associated with delayed initiation of effective MS therapies.

In 1975, 50-year-old Americans could expect to live slightly longer than most of their Western European counterparts. By 2005, American life expectancy had fallen behind that of most Western European countries. We find that this growing longevity gap is primarily due to real declines in the health of near-elderly Americans, relative to their Western European peers. We use a microsimulation approach to project what US longevity would look like, if US health trends approximated those in Western Europe. The model implies that differences in health can explain most of the growing gap in remaining life expectancy. In addition, we quantify the public finance consequences of this deterioration in health. The model predicts that gradually moving American cohorts to the health status enjoyed by Western Europeans could save up to $1.1 trillion in discounted total health expenditures from 2004 to 2050., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Focus groups provide a source of data that highlight community ideas on a topic of interest. How interview data will be utilized varies by project. With this in mind, we identify ways that focus group data from a particular population (Native American) articulate a health issue of individual tribal concern (alcohol consumption). Taking our analytic framework from linguistics, one of the four fields of inquiry in anthropology, we examine format ties and the performance of humor as stylistic features of tribal focus groups and illustrate how linguistic devices can be used in analyzing aspects of adolescent and adult drinking. Focus group data require systematic review and analysis to identify useful findings that can lead to inquiry points to initiate collaborative work with local experts before the data can be developed and configured into effective program initiatives.

This paper assesses how the relationship between health and educational attainment has changed over the last three decades. We examine trends in disease prevalence and self-reported health using the US National Health Interview Survey for five chronic conditions-arthritis, diabetes, heart disease, hypertension, and lung diseases. The sample is limited to non-Hispanic Whites ages 40-64 to focus on the value of education and not changing representation of minority populations. We find that health benefits associated with additional schooling rose over time by more than ten percentage points as measured by self-reported health status. This can be attributed to both a growing disparity by education in the probability of having major chronic diseases during middle age, and better health outcomes for those with each disease. The value of education in achieving better health has increased over the last 25 years; both in protecting against onset of disease and promoting better health outcomes amongst those with a disease. Besides better access to health insurance, the more educated increasingly adapted better health behaviors, particularly not smoking and engaging in vigorous exercise, and reaped the benefits of improving medical technology. Rising health disparities by education are an important social concern which may require targeted interventions., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

In this paper, we explore the role patient incentives play in slowing healthcare spending growth. Evidence suggests that while patients do indeed respond to financial incentives, cost-sharing does not uniformly improve value; rather, cost-sharing provisions must be deliberately structured and targeted to reduce care of low marginal value. Other mechanisms may be helpful in targeting particular populations or types of utilization. The spillover effects between privately insured and publicly insured populations as well as market imperfections suggest a potential role for public policy in promoting insurance design that slows spending growth while increasing the health that each dollar buys.

In September 2009, we released a set of concrete, feasible steps that could achieve the goal of significantly slowing spending growth while improving the quality of care. We stand by these recommendations, but they need to be updated in light of the new Patient Protection and Affordable Care Act (ACA). Reducing healthcare spending growth remains an urgent and unresolved issue, especially as the ACA expands insurance coverage to 32 million more Americans. Some of our reform recommendations were addressed completely or partially in ACA, and others were not. While more should be done legislatively, the current reform legislation includes important opportunities that will require decisive steps in regulation and execution to fulfill their potential for curbing spending growth. Executing these steps will not be automatic or easy. Yet doing so can achieve a healthcare system based on evidence, meaningful choice, balance between regulation and market forces, and collaboration that will benefit patients and the economy (see Appendix A for a description of these key themes). We focus on three concrete objectives to be reached within the next five years to achieve savings while improving quality across the health system: 1. Speed payment reforms away from traditional volume-based payment systems so that most health payments in this country align better with quality and efficiency. 2. Implement health insurance exchanges and other insurance reforms in ways that assure most Americans are rewarded with substantial savings when they choose plans that offer higher quality care at lower premiums. 3. Reform coverage so that most Americans can save money and obtain other meaningful benefits when they make decisions that improve their health and reduce costs. We believe these are feasible objectives with much progress possible even without further legislation (see Appendix B for a listing of recommendations). However, additional legislation is still needed to support consumers – including Medicare beneficiaries – in making choices that reduce costs while improving health.

Complex psychiatric disorders are resistant to whole-genome analysis due to genetic and etiological heterogeneity. Variation in resting electroencephalogram (EEG) is associated with common, complex psychiatric diseases including alcoholism, schizophrenia, and anxiety disorders, although not diagnostic for any of them. EEG traits for an individual are stable, variable between individuals, and moderately to highly heritable. Such intermediate phenotypes appear to be closer to underlying molecular processes than are clinical symptoms, and represent an alternative approach for the identification of genetic variation that underlies complex psychiatric disorders. We performed a whole-genome association study on alpha (alpha), beta (beta), and theta (theta) EEG power in a Native American cohort of 322 individuals to take advantage of the genetic and environmental homogeneity of this population isolate. We identified three genes (SGIP1, ST6GALNAC3, and UGDH) with nominal association to variability of theta or alpha power. SGIP1 was estimated to account for 8.8% of variance in power, and this association was replicated in US Caucasians, where it accounted for 3.5% of the variance. Bayesian analysis of prior probability of association based upon earlier linkage to chromosome 1 and enrichment for vesicle-related transport proteins indicates that the association of SGIP1 with theta power is genuine. We also found association of SGIP1 with alcoholism, an effect that may be mediated via the same brain mechanisms accessed by theta EEG, and which also provides validation of the use of EEG as an endophenotype for alcoholism.

Understanding inter-individual differences in stress response requires the explanation of genetic influences at multiple phenotypic levels, including complex behaviours and the metabolic responses of brain regions to emotional stimuli. Neuropeptide Y (NPY) is anxiolytic and its release is induced by stress. NPY is abundantly expressed in regions of the limbic system that are implicated in arousal and in the assignment of emotional valences to stimuli and memories. Here we show that haplotype-driven NPY expression predicts brain responses to emotional and stress challenges and also inversely correlates with trait anxiety. NPY haplotypes predicted levels of NPY messenger RNA in post-mortem brain and lymphoblasts, and levels of plasma NPY. Lower haplotype-driven NPY expression predicted higher emotion-induced activation of the amygdala, as well as diminished resiliency as assessed by pain/stress-induced activations of endogenous opioid neurotransmission in various brain regions. A single nucleotide polymorphism (SNP rs16147) located in the promoter region alters NPY expression in vitro and seems to account for more than half of the variation in expression in vivo. These convergent findings are consistent with the function of NPY as an anxiolytic peptide and help to explain inter-individual variation in resiliency to stress, a risk factor for many diseases.

It is an unresolved issue whether age or (expected) remaining life years better predicts health care expenditures. We first estimate a set of hazard models to predict life expectancy based on individual demographic characteristics and health conditions, and then use regression analyses to compare the predictive power of age and life expectancy in explaining health care expenditures. This paper differs from previous studies in that it uses predicted life expectancy to address the censoring of death; as a result, this paper goes beyond the large health care expenditures at the end of life and the results apply to both deceased and survivors. We find that age has little additional predictive power on health care expenditures after controlling for life expectancy, but the predictive power of life expectancy itself diminishes as health status measures are introduced into the model. These results are not of esoteric interest only for their statistical properties; we show that using life expectancy rather than age results in lower projections of future health care expenditures. This result suggests that increases in longevity might be less costly than models based on the current age profile of spending would predict.

We investigated the relation between diet pill use and eating disorder subtype, purging and other compensatory behaviors, body mass index (BMI), tobacco and caffeine use, alcohol abuse or dependence, personality characteristics, and Axis I and Axis II disorders in 1,345 participants from the multisite Price Foundation Genetics Studies. Diet pill use was significantly less common in women with restricting type of AN than in women with other eating disorder subtypes. In addition, diet pill use was associated with the use of multiple weight control behaviors, higher BMI, higher novelty seeking, and the presence of anxiety disorders, alcohol abuse or dependence, and borderline personality disorder. Findings suggest that certain clinical and personality variables distinguish individuals with eating disorders who use diet pills from those who do not. In the eating disorder population, vigilant screening for diet pill use should be routine clinical practice.

Background: The risk of schizophrenia is thought to be higher in population isolates that have recently been exposed to major and accelerated cultural change, accompanied by ensuing socio-environmental stressors/triggers, than in dominant, mainstream societies. We investigated the prevalence and phenomenology of schizophrenia in 329 females and 253 males of a Southwestern American Indian tribe, and in 194 females and 137 males of a Plains American Indian tribe. These tribal groups were evaluated as part of a broader program of gene-environment investigations of alcoholism and other psychiatric disorders., Methods: Semi-structured psychiatric interviews were conducted to allow diagnoses utilizing standardized psychiatric diagnostic criteria, and to limit cultural biases. Study participants were recruited from the community on the basis of membership in pedigrees, and not by convenience. After independent raters evaluated the interviews blindly, DSM-III-R diagnoses were assigned by a consensus of experts well-versed in the local cultures., Results: Five of the 582 Southwestern American Indian respondents (prevalence = 8.6 per 1000), and one of the 331 interviewed Plains American Indians (prevalence = 3.02 per 1000) had a lifetime diagnosis of schizophrenia. The lifetime prevalence rates of schizophrenia within these two distinct American Indian tribal groups is consistent with lifetime expectancy rates reported for the general United States population and most isolate and homogeneous populations for which prevalence rates of schizophrenia are available. While we were unable to factor in the potential modifying effect that mortality rates of schizophrenia-suffering tribal members may have had on the overall tribal rates, the incidence of schizophrenia among the living was well within the normative range., Conclusion: The occurrence of schizophrenia among members of these two tribal population groups is consistent with prevalence rates reported for population isolates and in the general population. Vulnerabilities to early onset alcohol and drug use disorders do not lend convincing support to a diathesis-stressor model with these stressors, commonly reported with these tribes. Nearly one-fifth of the respondents reported experiencing psychotic-like symptoms, reaffirming the need to examine sociocultural factors actively before making positive diagnoses of psychosis or schizophrenia.

According to Cloninger's model, type I alcoholics are thought to be innately vulnerable to anxiety and depression. In contrast, type II alcoholics are thought to have increased likelihood of antisocial personality disorder (ASPD) and reduced anxiety. However, allostatic activations of stress, anxiety, and dysphoria may be a common thread in alcohol use disorders (AUDs). Our aim was to find commonalities and differences in temperament of alcoholics with and without ASPD in three diverse populations. By sib-sib comparisons, we also evaluated the extent to which the temperament traits were moderated by familial factors including inheritance. We compared harm avoidance (HA), novelty seeking (NS), and reward dependence (RD) in alcoholics with ASPD, alcoholics without ASPD, and controls. Correlations for each temperament dimension were evaluated in pairs of siblings concordant and discordant for AUD. Participants were derived from three independent populations: Finnish Caucasians (N=453, men=100%, including a sample of alcoholic criminals), a Plains American Indian community sample (N=378; men=42%), and a subset of the familial and predominantly Caucasian Collaborative Study on the Genetics of Alcoholism (COGA) sample (N=967, men=47%). In all the three populations, both alcoholics with and without ASPD were higher in HA than controls. The increase of HA among alcoholics as compared to controls ranged from 54% to 12%. In two populations (COGA and Finns), NS was highest in alcoholics with ASPD, intermediate in alcoholics without ASPD, and lowest in controls. HA levels were correlated in sib-pairs concordant (either affected or unaffected) for AUD but not in discordant pairs. In conclusions, despite cultural diversity and different modes of ascertainment we found a consistent pattern of elevated HA in all groups of alcoholics, including alcoholics with ASPD. Even in alcoholics with long-term exposure to the anxiogenic effects of repeated cycles of alcohol withdrawal, genetic and other familial influences seem to play a role in moderating anxiety.

Variations in the gene encoding catechol-O-methyltransferase (COMT) are linked to individual differences in pain sensitivity. A single nucleotide polymorphism (SNP) in codon 158 (val(158)met), which affects COMT protein stability, has been associated with the human experience of pain. We recently demonstrated that three common COMT haplotypes, which affect the efficiency of COMT translation, are strongly associated with a global measure of pain sensitivity derived from individuals' responses to noxious thermal, ischemic, and pressure stimuli. Specific haplotypes were associated with low (LPS), average (APS), or high (HPS) pain sensitivity. Although these haplotypes included the val(158)met SNP, a significant association with val(158)met variants was not observed. In the present study, we examined the association between COMT genotype and specific pain-evoking stimuli. Threshold and tolerance to thermal, ischemic, and mechanical stimuli, as well as temporal summation to heat pain, were determined. LPS/LPS homozygotes had the least, APS/APS homozygotes had average, and APS/HPS heterozygotes had the greatest pain responsiveness. Associations were strongest for measures of thermal pain. However, the rate of temporal summation of heat pain did not differ between haplotype combinations. In contrast, the val(158)met genotype was associated with the rate of temporal summation of heat pain, but not with the other pain measures. This suggests that the val(158)met SNP plays a primary role in variation in temporal summation of pain, but that other SNPs of the COMT haplotype exert a greater influence on resting nociceptive sensitivity. Here, we propose a mechanism whereby these two genetic polymorphisms differentially affect pain perception.

The neuropeptide galanin (GAL) is widely expressed in the central nervous system. Animal studies have implicated GAL in alcohol abuse and anxiety: chronic ethanol intake increases hypothalamic GAL mRNA; high levels of stress increase GAL release in the central amygdala. The coding sequence of the galanin gene, GAL, is highly conserved and a functional polymorphism has not yet been found. The aim of our study was, for the first time, to identify GAL haplotypes and investigate associations with alcoholism and anxiety. Seven single-nucleotide polymorphisms (SNPs) spanning GAL were genotyped in 65 controls from five populations: US and Finnish Caucasians, African Americans, Plains and Southwestern Indians. A single haplotype block with little evidence of historical recombination was observed for each population. Four tag SNPs were then genotyped in DSM-III-R lifetime alcoholics and nonalcoholics from two population isolates: 514 Finnish Caucasian men and 331 Plains Indian men and women. Tridimensional Personality Questionnaire harm avoidance (HA) scores, a dimensional measure of anxiety, were obtained. There was a haplotype association with alcoholism in both the Finnish (P=0.001) and Plains Indian (P=0.004) men. The SNPs were also significantly associated. Alcoholics were divided into high and low HA groups (>or= and

Context: Tryptophan hydroxylase 2 (TPH2) encodes the rate-limiting enzyme for brain serotonin biosynthesis. It was recently reported that the TPH2 haplotype was linked to depression in humans., Objective: To determine the association of TPH2 with suicide attempt, major depression, and a neurochemical intermediate phenotype, cerebrospinal fluid 5-hydroxyindoleacetic acid., Design: We resequenced TPH2 coding, 5' promoter, 3'-untranslated region, and splice junction regions in 190 individuals selected for ethnic and clinical diversity, determined haplotype structure using 15 single nucleotide polymorphisms spanning 106 kilobases (kb), and performed linkage analysis in 1798 cases and controls representing 4 populations (657 African Americans, including 104 suicide attempters and 135 with major depression; 513 Finnish whites, including 150 suicide attempters; 146 US whites, including 81 with depression, anxiety disorder, or both; and 482 southwestern American Indians, including 123 suicide attempters and 191 with depression, anxiety disorder, or both) and in 94 Finnish whites for cerebrospinal fluid 5-hydroxyindoleacetic acid levels., Results: Sixteen single nucleotide polymorphisms, including Pro206Ser, were detected. The 15-locus panel defined and maximized information content from 2 haplotype blocks in whites, 3 haplotype blocks in African Americans, and the single haplotype block spanning TPH2 in southwestern American Indians. Among common Block1b haplotypes were 2 in yin and yang (opposite) configuration, indicating ancient origin. The yin haplotype, 212121, was increased in frequency in suicide attempters in both populations tested (Finnish whites and African Americans). It was associated with major depression and anxiety disorders in US whites and with major depression in African Americans. The yin haplotype was moderately predictive of lower cerebrospinal fluid 5-hydroxyindoleacetic acid concentrations in controls but not in cases., Conclusion: Haplotype linkage of TPH2 to suicide attempt and major depression and to a mediating phenotype, cerebrospinal fluid 5-hydroxyindoleacetic acid, provides preliminary evidence of a functional locus potentially within a haplotype block at least 52 kb in size.

Background: Histamine is expressed in cortical and limbic areas that are involved in emotion and cognition and modulates these behaviors. H1 receptor antagonists are sedative. Histamine N-methyltransferase (HNMT) catalyzes the Ntau methylation of histamine, the sole pathway for termination of the neurotransmitter action of histamine in mammalian brain. A common and functionally significant polymorphism, a C314T transition in exon 4 of the HNMT gene results in a Thr105Ile substitution of the protein encoded. The Thr105 allele is associated with approximately 2-fold higher enzyme activity, leading to the prediction that it might be associated with diminished histamine levels, resulting in differences in anxiety, cognition, and sedation that play important roles in alcoholism. In two ethnically distinct populations, we tested whether the Thr105Ile polymorphism was associated with alcoholism and with harm avoidance, a dimensional measure of anxious personality., Methods: A 5' exonuclease assay (TaqMan) was used to genotype Thr105Ile in psychiatrically interviewed Finnish Caucasian (n = 218) and Plains American Indian (n = 186) alcoholics, along with ethnically matched, psychiatrically interviewed, controls (Finns: n = 313, Plains Indian: n = 140)., Results: Ile105 allele frequencies were significantly lower in alcoholics compared with nonalcoholics in both populations (Finns: 0.12 vs. 0.17, chi(2) = 6, p = 0.015; Plains Indians: 0.03 vs. 0.08, chi(2) = 5, p = 0.023). Genotype distributions also differed significantly. In Finns, Ile105 showed borderline significance for an association with lower harm avoidance (p = 0.070) after correcting for alcoholism diagnosis., Conclusions: Decreased levels of brain histamine consequent to the Thr105 allele may result in higher levels of anxiety and, as a consequence, vulnerability to alcoholism.

The beta-adrenergic receptors (beta-AR) are G protein-coupled receptors activated by epinephrine and norepinephrine and are involved in a variety of their physiological functions. Previously, three beta-AR genes (ADRB1, ADRB2 and ADRB3) were resequenced, identifying polymorphisms that were used in genetic association studies of cardiovascular and metabolic disorders. These studies have produced intriguing but inconsistent results, potentially because the known functional variants: ADRB1 Arg389Gly and Gly49Ser, ADRB2 Arg16Gly and Gln27Glu, and ADRB3 Arg64Trp provided an incomplete picture of the total functional diversity at these genes. Therefore, we created marker panels for each beta-AR gene that included the known functional markers and also other markers evenly spaced and with sufficient density to identify haplotype block structure and to maximize haplotype diversity. A total of 27 markers were genotyped in 96 US Caucasians and 96 African Americans. In both populations and for each gene, a single block with little evidence of historical recombination was observed. For each gene, haplotype captured most of the information content of each functional locus, even if that locus was not genotyped, and presumably haplotype would capture the signal from unknown functional loci whose alleles are of moderate abundance. This study demonstrates the utility of using beta-AR gene haplotype maps and marker panels as tools for linkage studies on beta-AR function.

A significant proportion of the human genome is contained within haplotype blocks across which pairwise linkage disequilibrium (LD) is very high. However, LD is also often high between markers at more remote distances, and within different haplotype blocks. Here, we evaluate the origins of haplotype block structure in the three genes for alpha1 adrenergic receptors (alpha1-AR) in the human genome ( ADRA1A, ADRA1B and ADRA1D) by genotyping dense single-nucleotide polymorphism (SNP) marker maps, and show that LD signals between distant markers are due to the presence of extended haplotype superblocks in individuals with ancient chromosomes which have escaped historic recombination. ARs mediate the physiological effects of epinephrine and norepinephrine, and are targets of many therapeutic drugs. This work has identified haplotype backgrounds of alpha1-AR missense variants, haplotype block structures in US Caucasians and African Americans, and haplotype tag SNPs for each block, and we present strong evidence for ancient haplotype block superstructure at these genes which has been partially disrupted by recombination, and evidence for reinstatement of linkage disequilibrium by subsequent recombination events. ADRA1A is comprised of four haplotype blocks in US Caucasians, while in African Americans Block 1 is split. ADRA1B has four blocks in US Caucasians, but in African Americans only the first two blocks are present. ADRA1D has two blocks in US Caucasians, and the first block is replaced by two smaller blocks in African Americans. For both ADRA1A and ADRA1B, haplotype superstructures may represent a novel, higher-level hierarchy in the human genome, which may reduce redundancy of testing by further aggregation of genotype data.

The major inflammatory cytokines interleukin(IL)1beta, IL6 and tumor necrosis factor alpha (TNFalpha) play a crucial role in infection, inflammation and stress responses. Previously, three coding genes were resequenced, identifying promoter polymorphisms that were used in association studies of neurodegenerative diseases, metabolic disorders and cancer. These studies have produced intriguing but inconsistent results, potentially because the known functional variants: IL1B-511 C>T, IL6-174 G>C and TNF-308 G>A provided an incomplete picture of the total functional diversity at these genes. Therefore, we created marker panels for IL1B, IL6 and TNF/LTA that included the known functional marker but also other markers evenly spaced and with sufficient density to identify haplotype block structure and to maximize haplotype diversity. A total of 26 markers were genotyped in 96 US Caucasians and 96 African Americans. In both populations, a single block with little evidence of historical recombination was observed in IL1B, IL6 and TNF/LTA. For each gene, haplotypes captured the information content of each functional locus, even if that locus was not genotyped, and presumably haplotypes would capture the signal from unknown functional loci whose alleles are of moderate abundance. This study demonstrates the utility of using gene haplotype maps and marker panels as tools for linkage studies on related phenotypes.

The standardized evaluation of alcoholism and other psychopathologies in minority populations, particularly American Indians, has long been questioned. This study investigated the validity of one of the most commonly applied assessments for alcoholism--the Short Michigan Alcohol Screening Test (SMAST)--in two distinct American Indian tribal groups. We analyzed data collected from 1989 to 1995 from largely community representative samples of 456 Southwestern and 214 Plains Indians ages 21 or older. For comparison, alcohol dependence was diagnosed using Diagnostic and Statistical Manual of Mental Disorders, Third Edition-Revised (DSM-III-R) criteria from a detailed, modified version of the Schedule for Affective Disorders and Schizophrenia--Lifetime (SADS-L). Accuracy of the SMAST was quantified as sensitivity, specificity, likelihood ratios, and the area under the curve for receiver operating characteristics, using the DSM-III-R diagnosis as the reference. The standard SMAST cutoff score of > or = 3 had a demonstrated sensitivity 86% to 95%, but did not perform well in terms of specificity (23%-47%). Significantly higher cutoff scores (> or = 5 for both genders in the Southwestern tribe and 8 and > or = 6 for men and women in the Plains tribe) were required to demonstrate acceptable levels of specificity in both tribes. The findings suggest that the SMAST is not a valid tool to screen for alcohol misuse in these two tribal populations. The highly elevated and different thresholds required from one population to the next and from one gender to the next constitute a significant obstacle to the use of the instrument.

The norepinephrine transporter (NET) regulates levels of monoamine neurotransmitters integral to a variety of behaviors and autonomic functions. Two SLC6A2 polymorphisms have been used in genetic association studies, generating intriguing but nondefinitive results on traits such as hypertension and mood. One of these SLC6A2 variants is functional but rare. The other is common but not informative over the entire 48 kb SLC6A2 region and is insufficient to capture the functional diversity potentially contained within any SLC6A2 region. To elucidate SLC6A2 haplotype structure and define markers sufficient to capture haplotype diversity within detected haplotype blocks, 26 single-nucleotide polymorphisms (SNPs) were genotyped in 384 individuals evenly divided across Finnish Caucasian, US Caucasian, Plains American Indian, and African American populations. Three conserved blocks, 13.6, 12.5, and 25 kb in size and showing little evidence for historical recombination were observed in all populations. Haplotype diversity in block 1 and numbers of common haplotypes were highest in African Americans, among whom 5-6 optimal markers were sufficient to maximize diversity of each block. For other populations, 2-3 markers/block sufficed, but the optimal markers differed across populations. The SLC6A2 haplotype map and 25-marker panel (excluding the monomorphic one) is a comprehensive tool for genetic linkage studies on phenotypes related to NET function.

As policymakers consider expanding insurance coverage for the human immunodeficiency virus (HIV+) population, it is useful to ask whether insurance has any effect on health outcomes, and, if so, whether public insurance is as efficacious as private insurance in preventing premature death. Using data from a nationally representative cohort of HIV-infected persons receiving regular medical care, we estimate the impact of different types of insurance on mortality in this population. Our main findings are that (1) ignoring observed and unobserved health status misleads one to conclude that insurance may not be protective for HIV patients, (2) after accounting for observed and unobserved heterogeneity, insurance does protect against premature death, and (3) private insurance is more effective than public insurance. The better performance of private insurance can be explained in part by more restrictive Medicaid prescription drug policies that limit access to highly efficacious treatment.

Background: Alcohol abuse and alcoholism are leading causes of death among Native Americans. Little is known about the impact of negative childhood exposures, including parental alcoholism, childhood maltreatment, and out-of-home placement, on risk of lifetime DSM-IV (Diagnostic and Statistical Manual of Mental Disorders, 4th edition) diagnosis of alcohol dependence in this population., Methods: Face-to-face interviews were conducted with 1660 individuals from seven Native American tribes from 1998 to 2001. Logistic regression was used to estimate the impact of specific types and number of different adverse childhood experiences on alcohol dependence. Relationships between tribe-specific cultural characteristics and alcohol dependence were also examined., Results: There were significant tribal differences in rates of alcohol dependence and several adverse childhood exposures. Lifetime prevalence of alcohol dependence was high among all tribes (men: 21%-56%, women: 17%-30%), but one (men: 1%, women: 2%). High prevalence rates were documented for one or more types of adverse childhood experiences (men: 74%-100%; women: 83%-93%). For men, combined physical and sexual abuse significantly increased the likelihood of subsequent alcohol dependence (odds ratio [OR]=1.58; 95% confidence interval [CI], 1.10-2.27). For women, sexual abuse (OR=1.79; 95% CI, 1.21-2.66) and boarding school attendance increased the odds of alcohol dependence (OR=1.57; 95% CI, 1.03-2.40). Two separate patterns of dose-response relationships were observed for men and women. Significant inter-tribal differences in rates of alcohol dependence remained after accounting for tribe-specific cultural factors and geographic region., Conclusions: Effects of childhood exposures on high-risk behaviors emphasize screening for violence in medical settings and development of social and educational programs for parents and children living on and near tribal reservations.

Objective: Studies have shown that clinically ascertained alcoholics tend to have lower scores than nonalcoholics on cognitive performance tests, particularly the Block Design (BD) and Digit Symbol (DS) tests of the Weschler Adult Intelligence Scale-Revised (WAIS-R). The aim of this study was to determine whether similar differences are found in a community sample of Plains Indian men and women with an episodic pattern of drinking and a high lifetime prevalence of alcoholism (71% for men, 44% for women)., Method: We administered a truncated form of the WAIS-R to 334 members of a Plains Indian tribe (197 women and 137 men). Blind-rated psychiatric diagnoses were assigned according to Diagnostic and Statistical Manual of Mental Disorders, Third Edition (DSM-III-R) criteria and based on the Schedule for Affective Disorders, Lifetime Version (SADS-L) interview. We compared 68 currently drinking alcoholics (38 men and 30 women), 116 abstaining alcoholics (59 men and 57 women) and 150 nonalcoholics (40 men and 110 women)., Results: Current and past heavy drinking had no impact on WAIS-R scores in women. Male alcoholics who were abstinent > or = 2years had similar scores to nonalcoholic men. Male current drinkers showed a trend for lower overall verbal and performance (PIQ) scores and BD performance subtest. Further analysis showed that drinking for > or = 15 years was significantly associated with reduced DS in male current drinkers., Conclusions: These findings suggest that for the men in this community sample, the impact on PIQ is due to the direct effect of chronic alcohol consumption on cognitive performance and is at least partially reversible after 2 years of abstinence.