Safety of Risperidone for Acute Agitation and Alcohol Intoxication in Emergency Department Patients.

BACKGROUND: Acute agitation in the setting of alcohol intoxication is commonly encountered in the Emergency Department (ED). In this setting, expert consensus guidelines recommend haloperidol over second-generation antipsychotics due to their limited safety data in alcohol intoxication. OBJECTIVE: The primary objective was to compare vital sign changes prior to and after risperidone administration between ED patients presenting with alcohol intoxication [ETOH (+)] and without alcohol intoxication [ETOH (-)]. The secondary objective was to assess the effect of benzodiazepine co-administration with risperidone on vital signs. METHODS: This was a retrospective chart review of patients who received oral risperidone for acute agitation at two university EDs between January 1, 2012 and December 31, 2015. Vital signs (oxygen saturation, systolic and diastolic blood pressure, heart rate, and respiratory rate) were compared in patients who had ingested alcohol with those who had not. RESULTS: There were 785 patients without evidence of alcohol intoxication who received risperidone in the ED, and 52 patients with alcohol intoxication who received risperidone. Overall, risperidone with and without alcohol intoxication and benzodiazepine administration had no statistically significant effect on vital signs (p = ns for all comparisons). CONCLUSION: This study suggests that oral risperidone may be a safe option for acute agitation in patients presenting to the ED with alcohol intoxication.

Impact of a psychiatry elective on mental health stigma among pharmacy students.

BACKGROUND AND PURPOSE: Mental health stigma among healthcare providers remains a significant barrier to patients receiving optimal care for psychiatric conditions. This study's purpose is to evaluate the impact of a psychiatry elective on pharmacy students' attitudes toward patients with mental health disorders. EDUCATIONAL ACTIVITY AND SETTING: This study cohort included pharmacy students enrolled in a Special Topics in Psychiatry elective. Attitudes toward mental health disorders were measured at baseline (first day of class) and post-exposure (last day of class) using the 21-item Beliefs toward Mental Illness (BMI) Scale. Wilcoxon signed-rank tests were used to compare each component of the BMI scale as well as each subscale (dangerousness, poor social and interpersonal skills, and incurability) at baseline and post-exposure. FINDINGS: Fifty-eight pharmacy students (68% response rate) participated in this study. Most respondents were in their first year of the pharmacy program (44%), female (72%), and Asian (59%). There was a statistically significant decline in each BMI subscale at the end of the course: dangerousness, poor interpersonal and social skills, and incurability. There was no significant difference in mean change for the BMI sub-scores by gender, race, or personal experience with mental health disorders. SUMMARY: Incorporating a psychiatry elective into the pharmacy school curriculum can improve attitudes toward patients with mental health disorders. Future areas of research are warranted on the influence of specific components of a psychiatry elective that impact BMI scores and whether this translates to improved quality of care during clinical practice.

Medication use and driving patterns in older drivers: preliminary findings from the LongROAD study.

BACKGROUND: The potential for impaired driving due to medication use can occur at any age, though older adults are more likely to take multiple prescribed medications and experience side effects that may affect driving ability. The purpose of this study was to characterize the relationship between medications and driving safety behaviors. METHODS: Data for this study came from the five-site Longitudinal Research on Aging Drivers (LongROAD) project. Participants were active drivers, age 65-79 years at enrollment, and patients at one of the 5 participating sites. Medication names and doses were obtained at baseline based on the "brown-bag review" method. Medications were coded using the American Hospital Formulary Service system. Driving data were collected by a GPS accelerometer installed in the study participants' main vehicles. RESULTS: Medication data were available for 2949 (98.6%) of the 2990 participants, and 2898 (96.9% of all participants) had both medication data and at least 30 recorded days of driving. The median number of medications taken per study participant was seven, with a range of 0-51. Total number of medications was significantly associated with a higher rapid deceleration rate. Certain medication classes were significantly associated with other driving outcomes, including central nervous system agents (more speeding events), hormones and gastrointestinal medications (more rapid decelerations), electrolytes (fewer rapid decelerations), and antihistamines (greater right to left turn ratio). CONCLUSIONS: Older adult drivers are taking large quantities of prescription and non-prescription medications that may affect their driving safety. Certain medication classes are associated with potentially adverse driving patterns, such as speeding and rapid decelerations, while others are associated with potentially protective maneuvers, such as right hand turning. Further research is warranted to identify and mitigate potential adverse effects of such medications on driving safety in older adults.

Roles of binding elements, FOXL2 domains, and interactions with cJUN and SMADs in regulation of FSHß.

We previously identified FOXL2 as a critical component in FSHß gene transcription. Here, we show that mice deficient in FOXL2 have lower levels of gonadotropin gene expression and fewer LH- and FSH-containing cells, but the same level of other pituitary hormones compared to wild-type littermates, highlighting a role of FOXL2 in the pituitary gonadotrope. Further, we investigate the function of FOXL2 in the gonadotrope cell and determine which domains of the FOXL2 protein are necessary for induction of FSHß transcription. There is a stronger induction of FSHß reporter transcription by truncated FOXL2 proteins, but no induction with the mutant lacking the forkhead domain. Specifically, FOXL2 plays a role in activin induction of FSHß, functioning in concert with activin-induced SMAD proteins. Activin acts through multiple promoter elements to induce FSHß expression, some of which bind FOXL2. Each of these FOXL2-binding sites is either juxtaposed or overlapping with a SMAD-binding element. We determined that FOXL2 and SMAD4 proteins form a higher order complex on the most proximal FOXL2 site. Surprisingly, two other sites important for activin induction bind neither SMADs nor FOXL2, suggesting additional factors at work. Furthermore, we show that FOXL2 plays a role in synergistic induction of FSHß by GnRH and activin through interactions with the cJUN component of the AP1 complex that is necessary for GnRH responsiveness. Collectively, our results demonstrate the necessity of FOXL2 for proper FSH production in mice and implicate FOXL2 in integration of transcription factors at the level of the FSHß promoter.

Androgen receptor repression of gonadotropin-releasing hormone gene transcription via enhancer 1.

Gonadotropin-releasing hormone (GnRH) plays a major role in the hypothalamic-pituitary-gonadal (HPG) axis, and synthesis and secretion of GnRH are regulated by gonadal steroid hormones. Disruptions in androgen levels are involved in a number of reproductive defects, including hypogonadotropic hypogonadism and polycystic ovarian syndrome. Androgens down-regulate GnRH mRNA synthesis in vivo and in vitro via an androgen receptor (AR)-dependent mechanism. Methyltrienolone (R1881), a synthetic AR agonist, represses GnRH expression through multiple sites in the proximal promoter. In this study, we show AR also represses GnRH transcription via the major enhancer (GnRH-E1). A multimer of the -1800/-1766 region was repressed by R1881 treatment. Mutation of two bases, -1792 and -1791, resulted in decreased basal activity and a loss of AR-mediated repression. AR bound to the -1796/-1791 sequence in electrophoretic mobility shift assays, indicating a direct interaction with DNA or other transcription factors in this region. We conclude that AR repression of GnRH-E1 acts via multiple AR-responsive regions, including the site at -1792/-1791.

Androgen receptor repression of GnRH gene transcription.

Alterations in androgen levels lead to reproductive defects in both males and females, including hypogonadotropic hypogonadism, anovulation, and infertility. Androgens have been shown to down-regulate GnRH mRNA levels through an androgen receptor (AR)-dependent mechanism. Here, we investigate how androgen regulates expression from the GnRH regulatory region in the GT1-7 cell line, a model of GnRH neurons. A synthetic androgen, R1881, repressed transcription from the GnRH promoter (GnRH-P) in an AR-dependent manner, and liganded AR associated with the chromatin at the GnRH-P in live GT1-7 cells. The three known octamer-binding transcription factor-1 (Oct-1) binding sites in GnRH-P were required for AR-mediated repression, although other sequences were also involved. Although a multimer of the consensus Oct-1 binding site was not repressed, a multimer of the cluster of Oct-1, Pre-B cell leukemia transcription factor (Pbx)/Prep, and NK2 homeobox 1 (Nkx2.1) binding sites, found at -106/-91 in GnRH-P, was sufficient for repression. In fact, overexpression of any of these factors disrupted the androgen response, indicating that a balance of factors in this tripartite complex is required for AR repression. AR bound to this region in EMSA, indicating a direct interaction of AR with DNA or with other transcription factors bound to GnRH-P at this sequence. Collectively, our data demonstrate that GnRH transcription is repressed by AR via multiple sequences in GnRH-P, including three Oct-1 binding sites, and that this repression requires the complex interaction of several transcription factors.