Lorcaserin as a potential opioid-sparing adjunct

Opioids, such as oxycodone, morphine, and fentanyl, are commonly used medications in the treatment of moderate to severe pain. In spite of their efficacious analgesic properties, their increased prescribing rates by physicians and inherent abuse-related effects have led to the ongoing opioid epidemic. Their clinical utility is limited by the risk of adverse dose-dependent side effects, such as constipation and respiratory depression, and the development of tolerance and dependence. Opioid-sparing adjunctive therapies are sought to address these issues by reducing the dose of opioid needed to achieve analgesia through alternative non-opioidergic mechanisms and as a result, reduce the incidence of the previously mentioned side effects. Serotonin type-2C receptor agonists have demonstrated antinociceptive efficacy in preclinical models of chronic pain. Lorcaserin is a selective 5-HT2C receptor agonist and was reported to attenuate the abuse-related effects of oxycodone. The antinociceptive properties of 5-HT2C receptor agonists and their potential to alter the abuse-related effects of commonly abused drugs suggest that lorcaserin may be a potential opioid-sparing therapeutic. The goal of these studies was to evaluate the utility of lorcaserin, in combination with opioids, in a preclinical model of acute pain. Based on previous studies demonstrating the antinociceptive activity of 5-HT2C agonists, the hypotheses for these studies were that lorcaserin would increase the acute antinociceptive effects of opioids and would attenuate the development of tolerance associated with chronic opioid consumption. The results demonstrate that the acute antinociceptive effects and the time-course of activity of opioids were enhanced by doses of lorcaserin. These effects were mediated through activation of the 5-HT2C receptor and were not blocked by administration of naloxone. Additionally, the acute effects of lorcaserin to increase opioid potency and time course was not mediated through changes in opioid distribution in the blood or central tissues. Opioid tolerance was evaluated in vivo, and tolerance was developed using two methods of treatment: an acute (single dose administration) model of tolerance and a multiple-injection model. Testing the effect of lorcaserin in these models was important because current research suggests that the mechanisms that underlie both models of tolerance are distinct from one another. The results demonstrate that lorcaserin significantly blocked the development of acute tolerance in the whole animal and on a single cell level in dorsal root ganglion cell cultures. In the multiple-day tolerance model, lorcaserin partially attenuated the development of opioid antinociceptive tolerance. Chronic administration of an opioid is associated with desensitization of the MOR, and the effect of lorcaserin on opioid tolerance may be mediated through changes in MOR functional activity. Upon further investigation using agonist-stimulated [35S]GTPyS, the results showed that lorcaserin altered basal binding of [35S]GTPyS but not agonist-stimulated binding in mice that received chronic opioid treatment. These data suggest that the effect of lorcaserin on opioid tolerance, in the multiple-injection model, is not mediated through changes in MOR functional activity. Collectively, the tolerance studies suggest that the effect of 5-HT2C receptor activation by lorcaserin has differential effects on the stages of opioid tolerances and further supports the notion that the mechanisms that underlie the stages of opioid tolerance are distinct. Given the efficacy of lorcaserin to increase the acute antinociceptive effects of opioids and its ability to impair the development of opioid tolerance, collectively, these data suggest that lorcaserin may be a useful opioid-sparing adjunctive therapy

Trends and Disparities in TB among U.S.-born Black and White Chicago Residents, 1998-2008

ABSTRACT OBJECTIVE: To describe the decline of tuberculosis (TB) cases among U.S.-born non-Hispanic (NH) black and white Chicago residents. METHODS: Data from the National TB Surveillance System was used to analyze trends and characteristics of reported TB cases among U.S.-born NH black and U.S.-born NH white Chicago residents from 1998-2008. RESULTS: Chicago reported a total of 3,821 TB cases over the 11-year time period. Of these, 1,916 were U.S.-born NH black and 235 were U.S.-born NH white. The proportion of cases attributable to U.S.-born NH blacks was 63% (294/469) in 1998 and 34% in 2008 (72/213). Analysis for trends from 2000-2008 revealed a greater than predicted decrease in rates among U.S.-born NH blacks (p CONCLUSION: Despite more TB risk factors in Chicago’s U.S.-born black population, there was a narrowing of TB case disparity in Chicago from 1998-2008. Continued focused strategies aimed at controlling TB are needed

Patterns of Stepfamily Relationship Quality and Adolescents' Short-Term and Long-Term Adjustment

Stepfamilies experience unique dynamics, with implications for family functioning and youth well-being. Emerging research is incorporating a holistic perspective whereby stepfamily dynamics are viewed more comprehensively, and constellations of stepfamily relationship quality are identified. In the current study, we examined short-term and long-term associations between latent patterns of stepfamily relationships (including the quality of mother–child, stepfather–child, nonresident father–child, and stepcouple dyads) and youth adjustment (i.e., depression, delinquency, self-esteem) across three stages of youth development: adolescence, emerging adulthood, and young adulthood. Using a representative sample of adolescents from the National Longitudinal Study of Adolescent to Adult Health (Harris et al., 2009), results from longitudinal structural equation models and latent-growth curve models indicated that youth adjustment over time is optimized among youth in a residence-centered (i.e., high-quality relationships among mother–child, stepfather–child, and stepcouple dyads) or inclusive (i.e., high-quality relationships across all dyads, including the nonresident father) pattern, as compared with youth in an unhappy-couple (i.e., low-quality stepcouple relationship) or parent–child disconnection (i.e., low-quality relationships between youth and each parental figure) pattern. The results point to many similarities between male and female youth in terms of adjustment responses to patterns of stepfamily relationships, although some differences became apparent. In the context of stepfamily relationships marked by low-quality relationships, male youth might exhibit greater initial levels of externalizing problems than female youth, whereas female youth might exhibit greater initial levels of internalizing problems than male youth. Implications for future research and intervention and prevention efforts are discussed

Harnessing the strength of families to prevent social problems and promote adolescent well-being

The family context exerts notable influence on many domains of adolescent development and well-being. Recent research indicates that the family has the power not only to help youth get back on course after problems emerge, but that the family can also play a critical role in preventing problems for youth by reducing the severity of a problem or mitigating its occurrence. The purpose of this paper is to outline the promise and challenges of family-based approaches to prevention in social work practice. Research and theory have identified numerous risk and protective factors in the family. Prevention programs that address these risk and protective factors have shown strong evidence of reducing youth risky behavior. Program effects vary based on the strength of program implementation. Agencies often face barriers to implementation including maintaining model fidelity, engaging families, and sustaining funding. Implications for practice and policy are discussed

Day-to-day Consistency in Positive Parent–Child Interactions and Youth Well-Being

The frequency of positive parent–child interactions is associated with youth adjustment. Yet, little is known about daily parent–child interactions and how day-to-day consistency in positive parent–child interactions may be linked to youth well-being. Using a daily diary approach, this study added to this literature to investigate whether and how day-to-day consistency in positive parent–child interactions was linked to youth depressive symptoms, risky behavior, and physical health. Participants were youth whose parents were employed in the IT division of a Fortune 500 company (N = 129, youth’s mean age = 13.39, 55 % female), who participated in an 8 day daily diary study. Analyses revealed that, controlling for cross-day mean levels of positive parent–child interactions, older (but not younger) adolescents who experienced more consistency in positive interactions with parents had fewer depressive and physical health symptoms (e.g., colds, flu). The discussion focuses on the utility of daily diary methods for assessing the correlates of consistency in parenting, possible processes underlying these associations, and intervention implications

Daily parental knowledge of youth activities is linked to youth physical symptoms and HPA functioning.

Considerable evidence documents linkages between parental knowledge of youth activities and youth risky behavior. We extended this research to determine whether parental knowledge was associated with youth physical health, including reports of physical symptoms (e.g., headaches, stomachaches) and a biomarker of hypothalamic pituitary adrenocortical (HPA) axis functioning (i.e., salivary cortisol levels). Participants were children of employees in the Information Technology division of a Fortune 500 company (N = 132, Mean Age Youth = 13.39 years, 55% female) who participated in a daily diary study. Data were collected via telephone calls on eight consecutive evenings. On four study days, cortisol samples were collected at 4 time points (waking, 30 min after waking, before dinner, bedtime). Multi-level models revealed that, at the between-person level, youth whose parents had higher average knowledge about their activities, exhibited lower bedtime cortisol levels. Furthermore, at the within-person level, on days when parents displayed more knowledge than usual (relative to their own eight-day average), youth had lower before-dinner cortisol than usual. Linkages between average parental knowledge and physical health symptoms were moderated by youth age: Younger but not older adolescents whose parents were more knowledgeable had fewer physical health symptoms, on average. A next step is to identify the processes that underlie these associations

Stepfamily Relationship Quality and Children’s Internalizing and Externalizing Problems

The stepfamily literature is replete with between-group analyses by which youth residing in stepfamilies are compared to youth in other family structures across indicators of adjustment and well-being. Few longitudinal studies examine variation in stepfamily functioning to identify factors that promote the positive adjustment of stepchildren over time. Using a longitudinal sample of 191 stepchildren (56% female, mean age = 11.3 years), the current study examines the association between the relationship quality of three central stepfamily dyads (stepparent–child, parent–child, and stepcouple) and children's internalizing and externalizing problems concurrently and over time. Results from path analyses indicate that higher levels of parent–child affective quality are associated with lower levels of children's concurrent internalizing and externalizing problems at Wave 1. Higher levels of stepparent–child affective quality are associated with decreases in children's internalizing and externalizing problems at Wave 2 (6 months beyond baseline), even after controlling for children's internalizing and externalizing problems at Wave 1 and other covariates. The stepcouple relationship was not directly linked to youth outcomes. Our findings provide implications for future research and practice

Hostile Interactions in the Family: Patterns and Links to Youth Externalizing Problems

In line with family systems theory, we examined patterns of hostile interactions within families and their associations with externalizing problems among early-adolescent children. Using hostility scores based on observational data of six dyadic interactions during a triadic interaction (n = 462; i.e., child-to-mother, mother-to-child, child-to-father, father-to-child, mother-to-father, father-to-mother)—latent profile analysis supported three distinct profiles of hostility. The low/moderate hostile profile included families with the lowest levels of hostility across dyads; families in the mutual parent-child hostile profile scored higher on parent-child hostility, but lower on interparental hostility; the hostile parent profile showed higher levels of parent-to-child and interparental hostility, but lower child-to-parent hostility. Concerning links to youth outcomes, youth in the mutual parent-child hostile profile reported the highest level of externalizing problems, both concurrently and longitudinally. These results point to the importance of examining larger family patterns of hostility to fully understand the association between family hostility and youth adjustment