We have previously shown, however, that with ~weekly gaps between successive THC exposure, male and female rats do not become tolerant to the hypothermic effects of THC and nor does the magnitude differ across 20–25 weeks of adult age . In fact, it requires twice daily exposure to vapor inhalation for four days, at a minimum, to produce statistically significant acute tolerance . Furthermore, a lasting-tolerance inducing regimen of THC exposure during adolescence does not alter the intravenous self-administration of oxycodone which again suggests that cross tolerance/sensitization would not have resulted from the prior intermittent exposure of the animals to THC. It is likely that a similarly broad ranging set of studies would be required to parse the potential for intermittent acute heroin exposures similar to the present studies to induce plasticity of the response. For the present purposes of illustrating feasibility and dose control, however, such concerns are unlikely to affect the overall conclusions. Finally, opioids such as heroin suppress respiration at high doses, which might complicate the uptake of drug in an inhalation paradigm. This is unlikely to be the case for the present studies since a 7.5 mg/kg intravenous dose, or a 10 mg/kg intraperitoneal dose, fails to alter tidal volume in mice . A 90 mg/kg, i.p. dose was required to reduce tidal volume in the Hill et al. study and a toxicological report shows that 21.5 mg/kg, i.p. heroin is lethal to only 67% of rats . Animals in this study were not in clinical respiratory distress observable to expert research staff on removal from the inhalation chambers. Combined,vertical marijuana growing systems this evidence suggests that any ongoing respiratory effects of heroin were unlikely to be large enough to alter drug uptake across the session. This study reports a set of methods we have evolved from our ongoing experience using EDDS-based vapor exposure.
Through the developmental arc of this approach, it is clear that this is but one specific set of methods and that many variations are likely to also work in the hands of other interested laboratories. First, we have used several different iterations of ecigarette canister/atomizer and found that most differences are subtle in terms of drug delivery. There is a constantly changing and highly varied array of products available online and in local stores and most of them are likely to function for laboratory purposes. Effective vapor delivery can be achieved with many different types of cannister / atomizer products, with only modest methodological adjustments of puffing schedule, drug concentration and inhalation time. Second, the volume of the sealed chamber used to expose animals and the number per chamber can be varied, depending on the goals to be attained and the available equipment. The initial validation step is simply to determine that a vapor cloud to fill the available chamber volume can be produced. Third, while we have adopted a puffing schedule of every 5 minutes, more-, or less-frequent puffing could be used. The most important consideration for developing these methods is to have the ability to contrast and validate the effects of manipulating drug exposure parameters. Validation should be done with a desired target endpoint that is reliably produced in the relevant laboratory species/strain/ genotype by drug injection, or other route of drug administration. Once the target endpoint is determined, systematic manipulation of equipment, dosing protocols or drug concentrations can be used to achieve dose control. In 2017, suicide was the second leading cause of death among US adolescents, ages 12 to 17 years.
Further, approximately 17.2 percent of high school students reported having seriously considered making a suicide attempt in the past year, including 22.1% of female and 11.9% of male students.The rate of suicide among adolescents has increased substantially since 2000,3 with increases from 1.9 to 4.0 for adolescent girls and 6.6 to 9.6 for adolescent boys,and a concomitant increase in visits to emergency departments for adolescent suicidal behavior.These increases have occurred despite national prioritization of suicide prevention. Youth suicide risk factors encompass emotional, behavioral, and psychosocial concerns.A history of a previous suicide attempt or other self-harmful behavior predicts future attempts, and the risk for attempts increases with the frequency of previous self-harmful behavior.Depression is a risk factor for suicide attempts,repeat suicide attempts,and suicide.Alcohol abuse, drug use, and patterns of aggressive behavior are other primary risk factors.The risk of suicide attempts increases as substance use increases, and when substance use is associated with multiple risky behaviors.Moreover, the likelihood of repeated suicide attempts increases with the severity of aggressive/violent behavior and substance abuse.Childhood maltreatment, specifically sexual abuse, physical abuse, emotional abuse, and emotional neglect, has also been associated with suicide attempts in multiple studies.Many youth at elevated risk for suicide, including those who die by suicide, receive no mental health services.When MH services are obtained, this is often after the onset of suicidal behavior.Under-treatment is particularly prominent among racial and ethnic minority youth.Knowledge of the differing presentations or profiles of youth at high risk for suicide may help us to recognize youth for whom proactive screening is necessary for identification and subsequent intervention. Latent class analyses enables us to more systematically identify distinct profiles of risk, taking into consideration well-established risk factors for adolescent suicide. LCA is an approach that uses patterns of characteristics to identify mutually exclusive subgroups that are not directly observable . Previous studies have used LCA to examine profiles of youth suicide risk in primary care and school-based samples,and point to the importance of experiences such as sexual abuse.Psychological autopsy studies of youth who died by suicide, which entail interviews with significant others and review of social, legal, and medical records, also provide evidence for the existence of differing profiles.
In these studies, substance or alcohol abuse was more common among male participants and older adolescents,depression was more common among the female participants,conduct disorder was more common among male participants,and expressed suicidal intent was less common among younger adolescents who died by suicide.Previous studies have not, however, used a comprehensive inventory of behavior, mental health, substance use, adaptive functioning and social risk factors to develop distinct suicide risk profiles among youth seen in pediatric EDs. The objectives of this study are: to identify distinct profiles of youth at elevated risk for suicide, and to examine the association of these profiles with history of mental health service use . Study data are from the Emergency Department Screening for Teens at Risk for Suicide Study One cohort of 6,536 adolescents recruited from 13 pediatric EDs between June, 2015 and July, 2016.These EDs were members of the Pediatric Emergency Care Applied Research Network and spanned diverse geographic regions of the US. Recruitment was conducted during randomly assigned screening shifts. Among the 16,060 patients identified as study eligible, 10,554 patients were approached for possible study participation and 6,536 were recruited . Exclusion criteria were: ward of State, previously enrolled, non-English speaking, medically unstable, and severe cognitive impairment. Written informed consent and assent were obtained from parents and adolescents, respectively. Adolescents completed a self-report suicide risk survey,vertical rack system grow and parents completed a brief survey regarding their child’s behavioral problems, adaptive functioning, and MHSU. Adolescents received a $15 gift certificate for participation. Procedures were approved by each site’s Institutional Review Board.As a check on the baseline criteria for assignment in the “high risk” cell, which was a requirement for inclusion in LCA analyses for the present study, we calculated the association between baseline cell assignment and suicide attempt during the 6-month follow-up. We used LCA to identify latent classes underlying the observed data based on both continuous measures and binary indicators . The resulting classes are subgroups of adolescents who display similar patterns. Products of this analysis include estimates of the proportion having each categorical characteristic and the mean response for numeric measures within each latent class. We began by including six candidate variables: suicidal ideation, history of multiple suicide attempts, depression, aggression, alcohol use, and cannabis use, which we identified a priori as important for consideration based on the extant research literature.Next, other candidate variables were added to the model and assessed for theoretical fit and contribution to the model . Selection of final LCA model was made prior to any other analyses. LCAs were conducted in Mplus version 7.431 using the Mplus Automation package in R language and environment.We considered the possibility of up to six latent classes, limiting the total number to increase the likelihood that each class would characterize a meaningful percentage of adolescents. Full information maximum likelihood was used to handle missing data. Model fit was evaluated using Bayesian information criterion.
Summaries and statistical tests were performed using SAS software version 9.4.We compared latent classes with respect to demographics, then compared classes with respect to MHSU using single- and multi-variable logistic regression and adjusting for age, sex, race, and ethnicity. For these analyses, adolescents were placed in the latent class with the highest posterior probability of membership. Finally, we calculated univariable associations between the five latent class profiles for elevated suicide risk and suicide attempts during the 6- month follow-up period. Odds ratios and 95% confidence intervals are reported for these associations.In keeping with our first study objective, we identified five distinct profiles of suicide risk among adolescents presenting to pediatric EDs with elevated risk for suicide. These profiles were based on differing patterns of eight suicide risk factors: suicidal ideation, history of multiple suicide attempts, depression, impulsive-aggression, alcohol and drug use, and history of sexual and physical abuse. To our knowledge, this is the first study to use LCA to systematically address the heterogeneity of adolescent clinical presentations associated with elevated suicide risk. Moreover, in comparison to adolescents who were not designated as “high risk” at baseline, each “high risk” profile was associated with an increased likelihood of a suicide attempt within six months of the ED visit, supporting the validity of the “high risk” designation used to define this study’s sample. In keeping with our second study objective, we examined the association of these profiles with history of mental health service use . Results indicated that the likelihood of MHSU varied across risk profiles, suggesting that subgroups of adolescents at risk may either require proactive screening for suicide risk recognition or more proactive facilitation of engagement with MH services following recognition. Lifetime MHSU was the lowest, across types of services, for adolescents characterized by the HX-STB profile. Because 64% of these adolescents reported a history of suicide attempt and all of them met one or more criteria for high suicide risk at the time of their ED visit, this low rate of lifetime MHSU is concerning. It could be due to a perceived stigma associated with sharing past MH services as well as inadequate assessment and mental health linkage procedures in EDs currently, which has been documented.Other potential reasons for the low rate of lifetime MHSU include barriers associated with poverty; the shortage of child and adolescent psychiatrists; lack of parental awareness of youth mental health symptoms; and other family-related factors.The majority of adolescents in this study , all of whom screened positive for suicide risk, did not present to the ED with a psychiatric chief complaint. Moreover, the adolescents who matched profiles characterized by little or no current suicidal thoughts and no recent suicidal attempt were the least likely to present to the ED with a psychiatric complaint. This is despite the fact that the majority of these adolescents reported a previous suicide attempt, many reported a history of multiple suicide attempts, and nearly all reported a lifetime history of suicidal thoughts. Among adolescents characterized by the HX-STB+AGG profile, the co-occurrence of other suicide risk factors such as cannabis use, aggressive outbursts, sexual abuse was not uncommon.This is concerning and suggest the possible value of universal suicide risk screening. Given that approximately 19% of adolescents, ages 12 to 17 years, visit a hospital ED for services in a one-year period,the ED setting has substantial potential as a site for suicide risk screening and linkage to mental health services.