Racial and Ethnic Disparities in Pediatric Mental Health-Related Emergency Department Visits.

OBJECTIVES: To test the hypotheses that (1) rates of mental health-related concerns presenting to pediatric emergency departments (ED) have increased (2) rates are increasing more in minority than nonminority youth. METHODS: We performed a 5-year retrospective cohort study of youth with mental health-related ED visits using the Pediatric Health Information System. We calculated rates of mental health-related visits, in aggregate and by race/ethnicity. The Poisson model was used to generate incidence rate ratios of unique mental health-related visits each year using census data as the population denominator. RESULTS: There were 242,036 mental health-related visits that met the inclusion criteria, representing 160,656 unique patients. Approximately 7% of unique patients had 3 or more mental health-related visits, differing by race/ethnicity (8.75% non-Hispanic [NH]-Black vs 7.01% NH-White; adjusted odds ratio 1.14 [1.03, 1.26]). Overall, there were 42.8 mental health-related ED visits per 100,000 US children. The NH-Black children had higher rates of visits per 100,000 children compared with NH-Whites (66.1 vs 41.5; adjusted relative risk, 1.54 [1.50-1.59]). Mental health-related visits increased from 2012 to 2016 (33.31 [32.92-33.70] to 49.94 [49.46-50.41]). Every racial/ethnic group experienced an increase in rate of presentation over the study period; Hispanics experienced a significantly larger increase compared with NH-White children (P < 0.05). CONCLUSIONS: Mental health-related ED visits among children are increasing overall, disproportionally affecting minority children. The NH-Black children have the highest visit rates, and rates among Hispanics are increasing at a significantly higher rate when compared with NH-Whites. These results indicate need for increased capacity of EDs to manage mental health-related complaints, especially among minority populations.

The Impact of Health Messages on Maternal Decisions About Infant Sleep Position: A Randomized Controlled Trial.

Sudden infant death syndrome (SIDS) rates in African-Americans are more than twice national rates, and historically, African-American parents are more likely than other groups to place infants prone, even when they are aware of supine sleep recommendations. Prior studies have shown African-Americans have low self-efficacy against SIDS but high self-efficacy against suffocation. This study aimed to determine the impact of a specific health message about suffocation prevention on African-American parental decisions regarding infant sleep position. We conducted a randomized controlled trial of 1194 African-American mothers, who were randomized to receive standard messages about safe sleep practices to reduce the risk of SIDS, or enhanced messages about safe sleep practices to prevent SIDS and suffocation. Mothers were interviewed about knowledge and attitude, self-efficacy and current infant care practices when infants were 2-3 weeks, 2-3 months and 5-6 months old. Analyses of covariance were conducted to estimate the change in knowledge, attitudes and practice in each group, and chi square tests were used to compare sleep position with each variable. Over the first 6 months, the proportion of African-American infants placed supine gradually decreased and was unchanged by enhanced education about SIDS, suffocation risk and sleep safety. While initially high self-efficacy against SIDS and suffocation correlated with supine positioning, by 5-6 months self-efficacy did not correspond to sleep position in either group.

Regulation of Nephron Progenitor Cell Self-Renewal by Intermediary Metabolism.

Nephron progenitor cells (NPCs) show an age-dependent capacity to balance self-renewal with differentiation. Older NPCs (postnatal day 0) exit the progenitor niche at a higher rate than younger (embryonic day 13.5) NPCs do. This behavior is reflected in the transcript profiles of young and old NPCs. Bioenergetic pathways have emerged as important regulators of stem cell fate. Here, we investigated the mechanisms underlying this regulation in murine NPCs. Upon isolation and culture in NPC renewal medium, younger NPCs displayed a higher glycolysis rate than older NPCs. Inhibition of glycolysis enhanced nephrogenesis in cultured embryonic kidneys, without increasing ureteric tree branching, and promoted mesenchymal-to-epithelial transition in cultured isolated metanephric mesenchyme. Cotreatment with a canonical Wnt signaling inhibitor attenuated but did not entirely block the increase in nephrogenesis observed after glycolysis inhibition. Furthermore, inhibition of the phosphatidylinositol 3-kinase/Akt self-renewal signaling pathway or stimulation of differentiation pathways in the NPC decreased glycolytic flux. Our findings suggest that glycolysis is a pivotal, cell-intrinsic determinant of NPC fate, with a high glycolytic flux supporting self-renewal and inhibition of glycolysis stimulating differentiation.

Quantitative differences in HTLV-I antibody responses: classification and relative risk assessment for asymptomatic carriers and ATL and HAM/TSP patients from Jamaica.

Adult T-cell leukemia (ATL) and human T-cell lymphotropic virus type I (HTLV-I)-associated myelopathy/tropical spastic paraparesis (HAM/TSP) are known to be caused by HTLV-I infection. However, current methods used to determine HTLV-I infection do not differentiate between HTLV-I asymptomatic carriers (ACs) and ATL and HAM/TSP patients. Using the luciferase immunoprecipitation system, a highly sensitive, quantitative technology that can efficiently detect HTLV-I Ab responses, we examined Ab responses for HTLV-I in serum/plasma samples from 439 subjects in Jamaica, including HTLV-I-seronegative donors, ACs, and ATL and HAM/TSP patients. The Ab responses of HTLV-I-infected subjects differed significantly from those of seronegative donors for all 3 immunodominant proteins, Gag, Env, and Tax. HAM/TSP patients had significantly higher Ab responses for Gag and Env compared with ACs, and Ab responses for all 3 Ags were higher in HAM/TSP patients than in ATL patients. Moreover, immunoreactivities for HTLV-I Ags as determined by the luciferase immunoprecipitation system could distinguish HAM/TSP patients from ACs at a true-positive rate of 85.42% and from ATL patients at a true-positive rate of 75.00%, and modeled in conjunction with subject information to distinguish HAM/TSP patients from ACs (odds ratio = 14.12) and from ATL patients (odds ratio = 7.00). The relative risk assessment resulting from these significant differences between Ab responses in HTLV-I-infected groups may be a useful diagnostic tool in the future.

Humoral immune response to HTLV-1 basic leucine zipper factor (HBZ) in HTLV-1-infected individuals.

BACKGROUND: Human T cell lymphotropic virus type 1 (HTLV-1) infection can lead to development of adult T cell leukemia/lymphoma (ATL) or HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) in a subset of infected subjects. HTLV-1 basic leucine zipper factor (HBZ) gene has a critical role in HTLV-1 infectivity and the development of ATL and HAM/TSP. However, little is known about the immune response against HBZ in HTLV-1-infected individuals. In this study, we examined antibody responses against HBZ in serum/plasma samples from 436 subjects including HTLV-1 seronegative donors, asymptomatic carriers (AC), ATL, and HAM/TSP patients using the luciferase immunoprecipitation system. RESULTS: Immunoreactivity against HBZ was detected in subsets of all HTLV-1-infected individuals but the test did not discriminate between AC, ATL and HAM/TSP. However, the frequency of detection of HBZ-specific antibodies in the serum of ATL patients with the chronic subtype was higher than in ATL patients with the lymphomatous subtype. Antibody responses against HBZ were also detected in cerebrospinal fluid of HAM/TSP patients with anti-HBZ in serum. Antibody responses against HBZ did not correlate with proviral load and HBZ mRNA expression in HAM/TSP patients, but the presence of an HBZ-specific response was associated with reduced CD4+ T cell activation in HAM/TSP patients. Moreover, HBZ-specific antibody inhibited lymphoproliferation in the PBMC of HAM/TSP patients. CONCLUSIONS: This is the first report demonstrating humoral immune response against HBZ associated with HTLV-I infection. Thus, a humoral immune response against HBZ might play a role in HTLV-1 infection.

Evaluation of Communication and Safety Behaviors During Hospital-Wide Code Response Simulation.

INTRODUCTION: To understand the baseline quality of team communication behaviors at our organization, we implemented institution-wide simulation training and measured the performance of safety behaviors of ad hoc teams in emergent situations. METHODS: Clinicians participated in 2 interprofessional video-recorded simulation scenarios, each followed by debriefing. Using a standardized evaluation instrument, 2 reviewers independently evaluated the presence or absence of desired team safety behaviors, including escalating care, sharing a mental model, establishing leadership, thinking out loud, and identifying roles and responsibilities. We also scored the quality of sharing the mental model, closed-loop communication, and overall team performance on a 7-point scale. Discordant reviews were resolved with scoring by an additional reviewer. RESULTS: A total of 1404 clinicians participated in 398 simulation scenarios, resulting in 257 usable videos. Overall, teams exhibited desired behaviors at the following frequencies: escalating care, 85%; sharing mental models, 66%; verbally establishing leadership, 6%; thinking out loud, 87%; and identifying roles and responsibilities, 27%. Across all reviews, the quality of the graded behaviors (of 7 points) was 2.8 for shared mental models, 3.3 for closed-loop communication, and 3.2 for overall team performance. CONCLUSIONS: In a simulation setting with ad hoc teams, there was variable performance on completing safety behaviors and only a fair quality of graded communication behaviors. These results establish a baseline assessment of communication and teamwork behaviors and will guide future quality improvement interventions.

Smoking-induced change in intrasynaptic dopamine concentration: effect of treatment for Tobacco Dependence.

The aim of this study was to determine whether standard treatments for Tobacco Dependence affect smoking-induced changes in intrasynaptic dopamine (DA) concentration. Forty-three otherwise healthy adult cigarette smokers (10 to 40 cigarettes per day) were treated with either practical group counseling (PGC) psychotherapy (n=14), bupropion HCl (n=14), or matching pill placebo (n=15) (random assignment) for 8 weeks. Before and after treatment, each subject underwent a bolus-plus-continuous-infusion (11)C-raclopride positron emission tomography (PET) scanning session, during which he or she smoked a regular cigarette. The PET scanning outcome measure of interest was percent change in smoking-induced (11)C-raclopride binding potential (BP(ND)) in the ventral caudate/nucleus accumbens (VCD/NAc), as an indirect measure of DA release. Although the entire study sample had a smaller mean smoking-induced reduction in VCD/NAc BP(ND) after treatment (compared to before treatment), this change was highly correlated with smaller total cigarette puff volumes (and not other treatment variables). These data indicate that smoking-induced DA release is dose-dependent, and is not significantly affected by reductions in daily smoking levels or treatment type.

Brain nicotinic acetylcholine receptor occupancy: effect of smoking a denicotinized cigarette.

Our group recently reported that smoking a regular cigarette (1.2-1.4 mg nicotine) resulted in 88% occupancy of brain alpha4beta2* nicotinic acetylcholine receptors (nAChRs). However, this study did not determine whether nicotine inhalation or the many other pharmacological and behavioural factors that occur during smoking resulted in this receptor occupancy. If nicotine is solely responsible for alpha4beta2* nAChR occupancy from smoking, then (as estimated from our previous data) smoking a denicotinized (0.05 mg nicotine) or a low-nicotine (0.6 mg nicotine) cigarette (commonly used for research and clinical purposes) would result in substantial 23% and 78% alpha4beta2* nAChR occupancies, respectively, and a plasma nicotine concentration of 0.87 ng/ml would result in 50% alpha4beta2* nAChR occupancy (EC50). Twenty-four positron emission tomography sessions were performed on tobacco-dependent smokers, using 2-[F-18]fluoro-A-85380 (2-FA), a radiotracer that binds to alpha4beta2* nAChRs. 2-FA displacement was determined from before to 3.1 hours after either: no smoking, smoking a denicotinized cigarette, or smoking a low-nicotine cigarette. Analysis of this PET data revealed that smoking a denicotinized and a low-nicotine cigarette resulted in 26% and 79% alpha4beta2* nAChR occupancies, respectively, across three regions of interest. The EC50 determined from this dataset was 0.75 ng/ml. Given the consistency of findings between our previous study with regular cigarettes and the present study, nicotine inhalation during smoking appears to be solely responsible for alpha4beta2* nAChR occupancy, with other factors (if present at all) having either short-lived or very minor effects. Furthermore, smoking a denicotinized cigarette resulted in substantial nAChR occupancy.

The prevalence and significance of HTLV-I/II seroindeterminate Western blot patterns.

Human T-lymphotropic virus type I (HTLV-I) infects an estimated 15-20 million persons worldwide. A number of diseases have been associated with the virus including adult T-cell leukemia (ATL), HTLV-associated myelopathy/tropical spastic paraparesis (HAM/TSP), HTLV-I uveitis, and HTLV-I-associated infective dermatitis. Once it was shown that there is an increased risk for developing HAM/TSP associated with blood transfusion, screening for HTLV-1 among blood banks was implemented in Japan, United States, France, and the Netherlands. This process includes detection by an enzyme immunoassay (EIA) followed by a confirmatory Western blot (WB) in which recombinant proteins specific for HTLV-I Env glycoproteins are incorporated into WB strips. HTLV-I seropositive results are defined by the presence of antibodies against either gp46 or gp62/68 (both Env protein bands) and either p19, p24, or p53 (one of the gag bands). HTLV-II seropositivity is confirmed by the presence of rgp46-II. However, numerous cases have been documented in which serum samples are reactive by EIA, but an incomplete banding pattern is displayed by subsequent confirmatory WB. Although the significance of these HTLV-I/II seroindeterminates is unclear, it may suggest a much higher incidence of exposure to HTLV-I/II than previously estimated.

Effects of treatment for tobacco dependence on resting cerebral glucose metabolism.

While bupropion HCl and practical group counseling (PGC) are commonly used treatments for tobacco dependence, the effects of these treatments on brain function are not well established. For this study, 54 tobacco-dependent cigarette smokers underwent resting (18)F-fluorodeoxyglucose-positron emission tomography (FDG-PET) scanning before and after 8 weeks of treatment with bupropion HCl, PGC, or pill placebo. Using Statistical Parametric Mapping (SPM 2), changes in cerebral glucose metabolism from before to after treatment were compared between treatment groups and correlations were determined between amount of daily cigarette usage and cerebral glucose metabolism. Compared with placebo, the two active treatments (bupropion HCl and PGC) had reductions in glucose metabolism in the posterior cingulate gyrus. Further analysis suggested that PGC had a greater effect than bupropion HCl on glucose metabolism in this region. We also found positive correlations between daily cigarette use and glucose metabolism in the left occipital gyrus and parietal-temporal junction. There were no significant negative correlations between daily cigarette use and glucose metabolism. Our findings suggest that bupropion HCl and PGC reduce neural activity much as the performance of a goal-oriented task does in the default mode network of the brain, including the posterior cingulate gyrus. Thus, this study supports the theory that active treatments for tobacco dependence move the brain into a more goal-oriented state.

Ventral striatal dopamine release in response to smoking a regular vs a denicotinized cigarette.

Prior studies have demonstrated that both nicotine administration and cigarette smoking lead to dopamine (DA) release in the ventral striatum/nucleus accumbens. In tobacco-dependent individuals, smoking denicotinized cigarettes leads to reduced craving, but less pleasure, than smoking regular cigarettes. Using denicotinized cigarettes and (11)C-raclopride positron emission tomography (PET) scanning, we sought to determine if nicotine is necessary for smoking-induced DA release. Sixty-two tobacco-dependent smokers underwent (11)C-raclopride PET scanning, during which they smoked either a regular or denicotinized cigarette (double-blind). Change in (11)C-raclopride binding potential (BP) in the ventral striatum from before to after smoking was determined as an indirect measure of DA release. Cigarette craving, anxiety, and mood were monitored during scanning. Smoking a regular cigarette resulted in a significantly greater mean reduction in ventral striatal (11)C-raclopride BP than smoking a denicotinized cigarette. Although both groups had reductions in craving and anxiety with smoking, the regular cigarette group had a greater improvement in mood. For the total group, change in BP correlated inversely with change in mood, indicating that greater smoking-induced DA release was associated with more smoking-related mood improvement. Thus, nicotine delivered through cigarette smoking appears to be important for ventral striatal DA release. Study findings also suggest that mood improvement from smoking is specifically related to ventral striatal DA release.

Effect of a history of major depressive disorder on smoking-induced dopamine release.

BACKGROUND: Dopamine (DA) system dysfunction is implicated in the pathophysiology of major depressive disorder (MDD). We sought to determine if cigarette smokers with a history of MDD and current mild depressive symptoms have abnormal smoking-induced DA release (measured indirectly as change in (11)C-raclopride binding potential [BP(ND)]). METHODS: Fifty-six cigarette smokers either with (n = 10) or without (n = 46) a history of MDD (MDD+ and MDD-, respectively) underwent bolus-plus-continuous-infusion (11)C-raclopride positron emission tomography, during which they smoked a regular cigarette. Presmoking to postsmoking changes in (11)C-raclopride BP(ND) were compared between groups. Also, correlations were determined between change in BP(ND) and depression, anxiety, and withdrawal rating scale scores for the MDD+ group. RESULTS: The MDD+ group had a significantly greater reduction in (11)C-raclopride BP(ND) (-16.3%) than the MDD- group (-8.4%) (analysis of covariance [ANCOVA], p = .03). Significant negative correlations were found between depression/anxiety and change in (11)C-raclopride BP(ND) (r = -.77, p < .01 and r = -.74, p = .01, respectively). CONCLUSIONS: MDD+ smokers have greater smoking-induced DA release than MDD- smokers, and higher depression/anxiety levels are associated with greater smoking-induced DA release. These findings support the theory that MDD+ smokers have DA system dysfunction, including heightened smoking-induced DA release.