Background: Exposure to perfluorooctane sulfonic acid (PFOS) or to perfluorooctanoic acid (PFOA) increases mouse and human peroxisome proliferator–activated receptor alpha (PPARα) subtype activity, which influences lipid metabolism. Because cholesterol is the substrate from which testosterone is synthesized, exposure to these substances has the potential to alter testosterone concentrations. Objectives: We explored associations of total testosterone and sex hormone–binding globulin (SHBG) concentrations at age 15 years with prenatal exposures to PFOS, PFOA, perfluorohexane sulfonic acid (PFHxS), and perfluoronanoic acid (PFNA) in females. Methods: Prenatal concentrations of the perfluoroalkyl acids (PFAAs) were measured in serum collected from pregnant mothers at enrollment (1991–1992) in the Avon Longitudinal Study of Parents and Children (ALSPAC). The median gestational age when the maternal blood sample was obtained was 16 weeks (interquartile range, 11–28 weeks). Total testosterone and SHBG concentrations were measured in serum obtained from their daughters at 15 years of age. Associations between prenatal PFAAs concentrations and reproductive outcomes were estimated using linear regression models (n = 72). Results: Adjusted total testosterone concentrations were on average 0.18-nmol/L (95% CI: 0.01, 0.35) higher in daughters with prenatal PFOS in the upper concentration tertile compared with daughters with prenatal PFOS in the lower tertile. Adjusted total testosterone concentrations were also higher in daughters with prenatal concentrations of PFOA (β = 0.24; 95% CI: 0.05, 0.43) and PFHxS (β = 0.18; 95% CI: 0.00, 0.35) in the upper tertile compared with daughters with concentrations in the lower tertile. We did not find evidence of associations between PFNA and total testosterone or between any of the PFAAs and SHBG. Conclusions: Our findings were based on a small study sample and should be interpreted with caution. However, they suggest that prenatal exposure to some PFAAs may alter testosterone concentrations in females.

Introduction: The Aedes aegypti mosquito is responsible for the transmission of Yellow Fever, Dengue, Chikungunya and Zikavirus, making it a deadly vector and global public health threat. Zikavirus and Chikungunya, which were previously restricted to smaller geographic areas, have both appeared in the Western Hemisphere in the past three years and spread to areas where A. aegypti are present. This means that the pathogens have now entered areas in which the population has no previous immunity, which can lead to extensive outbreaks and epidemics. As the effects of global climate change become apparent, the areas of the globe that are suitable for inhabitance by A. aegypti may change. Additionally, this vector prefers human hosts for blood meals and requires standing water to breed, which is often created by water storage containers. This means that increasing urbanization and human population density are likely to put populations at higher risk of exposure to this vector. Methods: To create maps of the future risk of exposure to Aedes aegypti globally, species occurrence data for the vector and the Maxent modeling approach were used. Current and projected climate data were downloaded from WorldClim.org for the four representative concentration pathways (RCPs) used to model future climate change. Human population density, projected to 2050, the same timeframe as the future climate data, were used to model changes in human populations. To identify areas at high risk for future presence of A. aegypti populations, current and future models were compared across areas with at least a 50% probability of increased risk. These results where then used to create maps displaying high risk areas. Results: The AUC, an indicator of model fit, signaled that the models had high predictive power. However, high omission rates indicated that the trade-off of risk mapping may be a need to decrease probability thresholds below 50% to capture the full at-risk population. Future high-risk areas were most often those surrounding current cities, which supports the idea that the combination of urbanization and increasing human population density will work synergistically to increase the disease burden within and around urban centers. Additionally, expansion at the current geographic margins of this species shows that incursion into currently non-endemic areas is possible. Conclusions: Urban and peri-urban populations are likely to be at higher risk of exposure compared to rural areas due to global climate change and changes in population density. Attempts to model expansion of vector habitats should consider how these human population characteristics will change the risk to populations and how to best identify the areas at highest risk. Thresholds for the probability of a population being at risk of exposure to a vector may need to be different from those required to determine whether or not a habitat is suitable for a species. Appropriately determining which areas are high-risk results in maps and models can then be used to identify areas where climate change mitigation and vector control efforts are likely to have the highest impacts.

Background: Exposure to perfluorooctanoic acid (PFOA) and perfluorooctane sulfonic acid (PFOS) have been associated with higher circulating concentrations of total cholesterol (TC) and low density lipoprotein cholesterol (LDL-C). ApoB is the primary apolipoprotein component of LDL-C, and acts as a ligand for LDL-C receptors in various cells throughout the body. Circulating concentrations of ApoB are considered to be a better indicator of heart disease risk than TC or LDL-C. Objectives: Explore associations of concentrations of PFOA and PFOS with serum ApoB in adults. Methods: We analyzed data from 2744, 20-80 years old participants in the 2005–2006 National Health and Nutrition Examination Survey (NHANES). Linear regression models were used to estimate adjusted predicted means of serum ApoB (in g/L) for quartiles of PFOA and PFOS (in ng/mL) to describe patterns of associations. Results: Adjusted predicted mean concentrations of serum ApoB did not appear to vary meaningfully with increasing concentrations of PFOA (Q1 1.11, Q2 1.02, Q3 1.01, Q4 1.02) or increasing concentrations of PFOS (Q1 1.06, Q2 1.05, Q3 1.07, Q4 0.99) in study participants. Conclusions: Exposure to PFOA or PFOS does not appear to alter Apo B concentrations in adults.

Background: Rates of accidental overdose mortality from substance use disorder (SUD) have risen dramatically in the United States since 1990. Between 1999 and 2004 alone rates increased 62% nationwide, with rural overdose mortality increasing at a rate 3 times that seen in urban populations. Cultural differences between rural and urban populations (e.g., educational attainment, unemployment rates, social characteristics, etc.) affect the nature of SUD, leading to disparate risk of overdose across these communities. Methods: Multiple-groups latent class analysis with covariates was applied to data from the 2011 and 2012 National Survey on Drug Use and Health (n=12.140) to examine potential differences in latent classifications of SUD between rural and urban adult (aged 18 years and older) populations. Nine drug categories were used to identify latent classes of SUD defined by probability of diagnosis within these categories. Once the class structures were established for rural and urban samples, posterior membership probabilities were entered into a multinomial regression analysis of socio-demographic predictors' association with the likelihood of SUD latent class membership. Results: Latent class structures differed across the sub-groups, with the rural sample fitting a 3-class structure (Bootstrap Likelihood Ratio Test P value=0.03) and the urban fitting a 6-class model (Bootstrap Likelihood Ratio Test P valueThis result supports the hypothesis that different underlying elements exist in the two populations that affect SUD patterns, and thus can inform the development of surveillance instruments, clinical services, and prevention programming tailored to specific communities.

The IDSA Community-Acquired Pneumonia (CAP) Guideline recommends ceftriaxone in combination with doxycycline as an alternative to combination therapy with ceftriaxone and azithromycin for non-intensive care unit (ICU) patients hospitalized with CAP. This is an attractive alternative regimen due to recent concerns of increased cardiovascular risk associated with azithromycin. The objective of this study was to compare the clinical outcomes of azithromycin and doxycycline each in combination with ceftriaxone for non-ICU Veterans hospitalized with CAP.

Background: Community pharmacists are legally required to evaluate and confirm the legitimacy of prescription opioids (POs) prior to dispensing. Yet, previous research has indicated community pharmacists perceive nearly 50% of dispensed POs to be issued lacking a legitimate medical purpose. Objective: To analyze correlates of PO legitimacy judgments across pharmacist and pharmacy setting characteristics. Methods: A cross-sectional study of 2000 Tennessee pharmacists was conducted during October and November of 2012. Community pharmacists' self-reported attitudes, beliefs, and behaviors specific to PO legitimacy were elicited. Step-wise multinomial logistic regression techniques were used to model correlates of PO legitimacy across low, moderate and high PO legitimacy estimations. Results: Being female, practicing in a chain or independent practice setting, fear of employer disciplinary action if PO legitimacy is questioned, and self-confidence in one's ability to detect PO abuse increased the odds of low (vs. high) PO legitimacy estimation (p < 0.05). Employment in chain and independent pharmacies, having POs as a greater percent of total prescriptions filled, and having the perception of PO abuse as a problem in the practice setting were significant positive correlates of moderate (vs high) PO legitimacy estimation (p < 0.05). Conclusions: Both modifiable and non-modifiable correlates were statistically significantly associated with PO legitimacy judgments. Distinct correlates were noted across low and moderate as compared to high estimations of PO legitimacy. Legitimacy judgments can inform theoretical exploration of PO dispensing behaviors and inform intervention development targeted at reducing and preventing prescription drug abuse.

Background: Community pharmacists are a key intervention point in efforts to prevent and mitigate the impact of prescription drug abuse and misuse (PDA/M); yet pharmacists' perceptions regarding PDA/M have been explored only briefly in the literature. Objectives: 1) To explore Tennessee community pharmacists' perceptions regarding opioid pain reliever (OPR) prescribing, dispensing and abuse; 2) to explore community pharmacists' self-efficacy beliefs regarding PDA/M-specific communication; and 3) to evaluate perceived barriers to engaging patients in PDA/M-specific communication. Methods: A 55-item survey instrument was developed using the Theory of Planned Behavior (TpB) as a theoretical framework. Questionnaires were mailed to a stratified sample of 2000 licensed Tennessee pharmacists using the Tailored Design Method of survey administration during October and November, 2012. Results: A response rate of 40% was obtained. A majority of pharmacists (87.5%) perceived OPR abuse to be a problem in their practice settings. On average, a little more than half (53%) of prescriptions issued for OPRs were estimated to be for patients with one or more legitimate medical reasons justifying the medication(s). A small fraction of pharmacists (13%) reported having addiction treatment facility information in their practice settings, and only a small percent reported strong self-efficacy beliefs regarding PDA/M patient communication. Job-related time constraints were perceived as the primary barrier to engaging in PDA/M communication. Conclusions: Community pharmacists in Tennessee are aware of PDA/M by patients receiving opioid prescriptions and value their role in communicating with these patients but indicate their ability to do so effectively is hindered by a lack of confidence, training, and time. Further research to identify and test methods for facilitating PDA/M communication by pharmacists is indicated.

Worldwide, alcohol is the third leading risk factor for disease burden, while its harmful use leads to 2.5 million deaths every year. Alcohol dependence (AD) is a complex disease, with devastating effects on individuals, families, and society. It is estimated that 76.3 million people worldwide have suffered from alcohol use disorders (AUD), including alcohol abuse and AD. Alcohol withdrawal or alcohol withdrawal symptom (AWS) refers to a cluster of symptoms that may occur when a heavy drinker suddenly stops or significantly reduces their alcohol intake. These symptoms can start as early as 2 h after the last drink, persist for weeks, and range from mild anxiety and shakiness to severe complications, such as seizures and delirium tremens. Family, twin, and adoption studies have indicated that genetic and environmental factors and their interactions contribute to the development of AD and related phenotypes, with a heritability coefficient of more than 0.5 for AD. Whole-genome linkage and candidate gene association studies have successfully identified several chromosome regions and genes that are related to AD and AWS. Furthermore, gene expression analysis, epigenetic studies, and genome-wide association studies (GWAS) have provided regions and loci for AWS. This chapter reviews the recent findings in genetic studies of AWS.

Background: Over the long term, unhealthy lifestyles can lead to many health problems, especially type 2 diabetes (T2D). The aim of the present study was to determine associations between lifestyle factors (smoking, alcohol consumption, physical activity, and diet) and T2D in American adults (aged ≥20 years) in a nationally representative sample. Methods: Data for 12 987 American adults participating in the National Health and Nutrition Examination Survey 2005–2014 were evaluated. Weighted multiple logistic regression models were used to examine associations between the four lifestyle factors and T2D after adjusting for demographics and socioeconomic status (SES). Prevalence trends for T2D were examined using Cochran–Armitage tests. Results: There was a significant increasing prevalence trend for T2D among American adults. Smokers and individuals consuming >12 alcoholic drinks in the past year were less likely to report having T2D than non‐smokers (odds ratio [OR] 0.41; 95% confidence interval [CI] 0.35–0.48) and those consuming(OR 0.46; 95% CI 0.39–0.55). Participants with light physical activity have a greater likelihood of having T2D than those engaging in vigorous physical activity (OR 5.72; 95% CI 4.30–7.60). Individuals consuming a poor diet were more likely to report having T2D than those eating an excellent diet (OR 1.18; 95% CI 1.02–1.41). All these relationships remained significant after adjustment for demographics and SES. Conclusion: All four lifestyle factors were significantly associated with T2D among American adults. The findings of the present study provide useful information for healthcare providers that may help them promote specific lifestyle modifications.

Introduction: Increased vegetable intake has been shown to protect against metabolic syndrome (MetS) among adults. However, limited studies have examined the association between vegetable consumption and MetS among pediatric Hispanic populations. The objective of this study was to explore the association between vegetable consumption and being at risk for MetS among a pediatric Hispanic population of Northeast Tennessee (TN). Methods: Nutrition, parental, and blood sample data were obtained from 114 Hispanic children aged 2 to 10 years who received care from a community health center in Northeast TN. Being at risk for MetS included having two or more of the following: elevated waist circumference, high blood pressure, elevated triglycerides, and low HDL. Multiple logistic regression analysis was used to examine the association between vegetable consumption and being at risk for MetS while controlling for child age, child sex, and parental marital status. Results: Higher vegetable intake was found to be associated with a 60% decrease in odds of being at risk for MetS (95% Confidence Interval (CI): 0.16-0.99). Children of parents who were not married were 162% more likely to be at risk for MetS compared to children of parents who were married (95% CI: 1.17-5.88). Discussion: Higher vegetable intake was associated with decreased odds of being at risk for MetS among this Hispanic pediatric population. Additional studies with a larger sample size are warranted to further understand the relationship of vegetable consumption and their potential protective effects on the development of MetS among this population.