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Of particular interest to this study is a common polymorphism involving a Val to Met substitution at codon 158. The Val allele of the COMT Val158Met polymorphism is 40% more enzymatically active than the Met allele. Thus, carriers of the Met allele metabolize dopamine at a less efficient rate, resulting in higher levels of dopamine in the synapse and ultimately an escalation in dopamine receptor activation. This differentiation of dopamine receptor activity dependent on COMT genotype has led to several investigations into the relationship between COMT and executive dysfunction in which the Val allele has been putatively linked to poor performance on executive functioning tasks. However, to our knowledge no work has examined the relationship between COMT and sexual risk behavior; albeit studies of similar behaviors such as novelty seeking, reward dependence, as well as affective arousal and regulation have demonstrated significant relationships. Given the aforementioned paucity of research in the current literature addressing the contribution of genetic and neurocognitive factors on sexual risk behavior, the primary aim of this study was to examine the main effects of executive functioning as well as the main effects of the COMT Val158Met polymorphism on sexual risk behavior among a ethnically diverse population of men with and without METH dependence and/or HIV infection. Within this aim, we hypothesized that the highly active COMT Val/Val genotype and its putatively associated deficits in executive functioning would be independently associated with sexual risk behaviors. In addition, as a result of previously mentioned research that has demonstrated an association between COMT genotype and executive functioning we also explored the potential interaction effects of COMT and executive dysfunction on sexual risk behavior.Participants were volunteers evaluated at the HIV Neurobehavioral Research Center at the University of California in San Diego as part of a cohort study focused on central nervous system effects of HIV and methamphetamine. The current study comprised 192 sexually active non-monogamous men with and without methamphetamine dependence and/or HIV infection . Men were classified as nonmonogamous if they stated they had “no current partner” at time of assessment. Monogamous men were excluded because unsafe sexual behavior within a monogamous relationship is less risky than in non-monogamous relationships.

All participants underwent a comprehensive characterization procedure that included collection of demographic, neuromedical,hydroponic rack system psychiatric as well as neuropsychiatric information. HIV serological status was determined by enzyme linked immunosorbent assays plus a confirmatory test. Lifetime METH dependence was determined by the Structured Clinical Interview for the Diagnostic and Statistical Manual of Mental Disorders Version IV . However, participants were not actively using other substances, with the exception of cannabis and alcohol. Potential participants were excluded if they met lifetime dependence criteria for other drugs, unless the dependence was judged to be remote and episodic in nature by a doctoral level clinician. Alcohol dependence within the last year was also an exclusion criterion. All participants were seronegative for hepatitis C infection. Additional information for each participant was collected as it relates to current depressed mood as well as lifetime diagnosis of Major Depression Disorder and/or Bipolar Disorder I or II. Current depressed mood was assessed utilizing the Beck Depression Inventory-I and MDD and Bipolar Disorder were ascertained using the SCID-IV. Information was also collected to determine lifetime dependence on sedatives, cannabis, opioids, cocaine,hallucinogens, and alcohol, using the SCID-IV. For METH+ participants, additional information was collected regarding age at first use, years of use, and days since last use of METH; whereas for HIV+ participants, HIV RNA plasma copies was ascertained as part of a larger neuromedical evaluation. All participants gave written consent prior to enrollment and all procedures were approved by the Human Research Protection Program of the University of California, San Diego and San Diego State University.Executive functioning was determined as part of a larger comprehensive battery of tests covering seven ability domains . The executive functioning domain deficit score, of particular focus in this study, was made up of perseverative responses on the Wisconsin Card Sorting Test; errors on the Halstead Category Test, which measures abstraction and cognitive flexibility; and time to complete the Trail Making Test part B, reflecting ability to switch and maintain attention between ongoing sequences.

Raw scores for each of these component tests were converted to demographically-adjusted T-scores , including adjustments for age, education, gender, and ethnicity as available for each test. The demographically adjusted T-scores for each test were then converted into deficit scores, which reflect degree of impairment by setting performances within the normal range at zero with a range from 0 to 5 . Finally, the individual deficit scores were averaged to derive the domain deficit score, which reflects the severity of executive functioning deficit. Previous work has demonstrated that deficit scores achieve good diagnostic agreement with classifications made by blind clinical ratings. All neurocognitive testing and scoring was performed by trained psychometrists blinded to participants’ genotypes.A multiplex PCR technique designed using Sequenom SpectroDESIGNER software was employed by inputting a sequence containing 100 bp of flanking sequence on either side of the COMT Val158Met polymorphism. The SNP was then grouped into multiplexes so that the extended product would not overlap in mass with any other oligonucleotide present in the reaction mix, and where no primer-primer, primer-product, or nonspecific interactions would occur. The PCR was carried out in 384-well reaction plates in a volume of 5 μl using 10 ng genomic or whole-genome amplified DNA. All subsequent steps, up until the reaction, were spotted onto the SpectroCHIP and carried out in the same reaction plate. After PCR, any unincorporated dNTPs from the PCR were removed from the reaction by digestion with Shrimp alkaline phosphatase. dNTPs were removed so that they could not play any role in the extension of the oligonucleotide at the SNP site. The extension reaction was then carried out in the presence of the extension oligonucleotide and a termination mix containing mass-modified dideoxynucleotides which extended the oligonucleotide over the SNP site with one base. Before spotting onto the SpectroCHIP, the reaction was cleaned by incubation with a cation-exchange resin which removed any salts present. The extension product was then spotted onto a 384-well spectroCHIP before being flown in the MALDI-TOF mass spectrometer. Data were collected, in real time, using SpectroTYPER Analyzer 3.3.0.15, SpectraAQUIRE 3.3.1.1 and SpectroCALLER 3.3.0.14 algorithms.

All statistical tests and procedures were conducted using SPSS 10.0 . Univariate comparisons across the three COMT genotypes were performed using one-way analysis of variance for continuous and chi-squared tests for categorical variables. In cases, where data violated normality assumptions medians were calculated and nonparametric tests performed. To examine the main and explore the interaction effects of executive functioning and COMT on sexual risk behaviors, hierarchical multiple linear regressions in accord with Barron and Kenny’s approach were conducted for each of the seven sexual risk behaviors under study. Prior to running each analysis, the executive functioning variable was centered and the COMT genotype contrast coded to reduce problems resulting from multi-collinearity . In addition, interaction terms were created by multiplying COMT genotype by the centered executive functioning variable. Next, multiple linear regressions were used to examine potential confounders based on univariate genotype comparisons described above. These confounders included: ethnicity, METH status, HIV status and age at first intercourse. We also included BDI scores based on inclusion of this measure in recent work testing a similar hypothesis. Results showed that METH status, HIV status,rolling benches canada and age at first intercourse accounted for a significant unique variance for all sexual behaviors under investigation . Thus to control for these potential confounding effects, the residuals derived from each of the sexual behavior models were used as the dependent variables for all subsequent regression models. The centered executive functioning variable and COMT genotype as well as the new interaction term were then entered as independent variables into seven individual hierarchical multiple regression models using the residuals described above as the dependent variable. For models in which a significant interaction was observed, a final round of regressions were conducted stratified by COMT genotype to determine the nature of the interaction between executive functioning and COMT on the particular sexual risk behavior. Due to the exploratory nature of the interaction analysis we selected a relaxed alpha threshold alpha < .10 to reduce Type II errors, albeit the traditional alpha threshold of .05 was used for all other analyses.To our knowledge this study is the first to examine main effects as well as explore the interaction effects of COMT genotype and executive functioning on sexual risk behavior. Our main findings suggest significant executive dysfunction main effects for number of sexual partners as well as frequency of oral sex and condom use. In addition, results of our exploratory interaction analyses provide evidence that COMT genotype and executive dysfunction interact in models of number of sexual partners, condom use, insertive and receptive anal sex, as well as oral sex. Stratified analyses further suggest that the strength of these associations is dependent on the number of Met alleles the individual was carrying, with the exception of oral sex in which Val/Val was the informative genotype. Our significant executive dysfunction main effects for sexual risk behaviors are discordant with the only other study, to our knowledge, that has examined the association between executive dysfunction and sexual risk behavior. In that study, no association was found between executivedys function and sexual risk behavior among an African American sample of men and women poly-substance abusers with and without HIV infection. However, three major methodological differences may explain our discordant findings. First, Gonzalez et al.estimated sexual risk behavior in the past 6 months compared to our window of 12 months and also utilized a composite score rather than individual sexual risk behaviors as their dependent variable. Second, executive dysfunction was assessed using the Iowa Gambling Task, delayed non-matching to sample paradigm, and Stroop task-reaction time version which, respectively, measure decision-making, working memory, and response inhibition. Although these tests are well justified, other components of executive functioning such as perseveration, cognitive sequencing, and concept formation which were assessed in the current study, were not examined.

Third and finally, regression models were adjusted for sensation seeking, a factor shown in previous research to be associated with sexual risk behavior [34–37]; however, in the current study sensation seeking data was not available and was not adjusted for. Thus, future work examining the association between executive dysfunction and sexual risk behaviors are warranted; particularly research utilizing larger samples with diverse measures of executive functioning and models adjusting for sensation seeking and other personality covariates. Novel to the current study, we demonstrated several genotype by endophenotype interactions for sexual risk behaviors. A relaxed significance criterion produced significant interactions for number of sexual partners, condom use, insertive and receptive anal sex, as well as oral sex. These interactions collectively advocate for further investigation of genotypeendophenotype interactions for sexual risk behavior. However, due to the exploratory nature of these interactions our discussion will be confined to interactions observed for number of sexual partners, frequency of insertive anal sex and condom use, as interactions observed in these models met the traditional significance criterion . We observed both a main and interaction effect for number of sexual partners, albeit only within the model including the composite executive functioning deficit score. In this model we found that among carriers of the Met allele , a positive association between executive functioning deficit and number of sexual partners was present. Thus, among Met allele carriers those with greater deficit scores reported greater number of sexual partners; whereas among Val/Val carriers this association was not significant. Similar to results for number of sexual partners, stratified analysis showed that among carriers of the Met/Met but not Val/Met or Val/Val genotype an positive association between executive dysfunction and frequency of insertive anal sex was present, although only statistically significant for models including the Trails B test. Thus, individuals with lower T-scores on Trails B reported greater frequency of insertive anal sex only if they were carriers of the Met/Met genotype. Finally, the strongest interaction observed was between COMT and the Halstead Category Test for frequency of condom use. Contrary to the expected association, results suggest a negative association among carriers of the Met/Met genotype in which lower T-scores on the Category Test was associated with an increased frequency of condom use.

We have observed participants with only one transient episode of cutting, those in which it is habitual and compulsive and those who have had on-and-off periods of cutting with varying durations. This periodicity may occur either because conditions of stress may wax and wane or because the relieving effect of the cutting endures for a period of time before it in effect needs to be renewed. Episodes of cutting may be situational or habitual. An instance of the former is a girl who, although she had been cutting herself periodically for several years, indicated that a recent episode was in relation to the conjunction of her grandfather dying and her boyfriend breaking up with her. A habitual instance is the boy who used a pencil or a toothpick as his instruments, though according to his mother he scratched but never broke his skin. He said, “Two months ago I started cutting myself. I just couldn’t stop cutting myself. I had the opportunity to do it, I couldn’t help it . . . sometimes it’s just no reason, other times, it’s just because I want to. It’s because I feel like it.” Notably, this boy indicated that the cutting did not make him feel better. The intentionality of cutting is complex, and as was the case among SWYEPT participants, cutting may be associated with other forms of self-harm such as head-banging, self-choking, bulimia, eraser burns, or drug abuse. The motivations typically reported for cutting in this study were depression, anger, frustration, stress, and tension. The intended results included relief, to feel good, to feel pain, to hurt oneself,hydroponic tables canada and to see the blood. Notably, three of the participants reported that cutting did not make them feel better. With respect to integration of cutting into one’s identity as a mode of self-orientation, it was more common to hear that a young person “started cutting,” “cut myself,” or even “ended up cutting,” but there were instances of girls and a boy who declared either that “I am a cutter” or “I was a cutter.”

The only other study of intentionality among adolescent inpatient cutters we have been able to identify used the self-injury motivation scale II developed by Osuch, Noll, and Putnam , which taps factors including affect modulation, desolation, punitive duality, influencing others, magical control, and self-stimulation. The researchers found that the mean number of reasons cited for cutting themselves was 20 out of the 36 listed in the instrument as contributing to these factors and that 56% described their cutting as impulsive while 60% reported feeling emotional relief after cutting . Notably, males and females cited comparable reasons for self-injury, with a trend for females to use cutting for controlling negative affects more than males . Self-cutting is also not invariably linked to suicidality. Among girls who were SWYEPT participants, 18 reported suicidality, and 17 reported cutting; three of the cutters were not suicidal, and four of the suicidal girls were not cutters. Among boys, 14 participants reported suicidality, and 10 reported cutting; three cutters were not suicidal, and seven of the suicidal boys were not cutters. Moreover, cutting was by no means the only or the most common method for suicide attempts by participants. In this respect, we note the study by Gulbas et al.which expressly focuses on the relation between suicidal behavior and nonsuicidal self-injury among Latina adolescents in the United States.Gulbas and colleagues identify a series of factors relevant to both NSSI and suicide that correspond to features we found among the SWYEPT participants, including family fragmentation, conflict, physical and sexual abuse, and domestic violence. The relationships among these factors are complex and are found cross-culturally, though they tend to be more severe with suicide than with NSSI . Given the multiple challenges faced by our study participants in New Mexico, and the extraordinary conditions that define the contours of struggle for coherence in their lives, a focus on the specific act of cutting offers a necessarily limited but existentially critical insight into the nature of their experience. Without a doubt this requires attending to the question of children’s agency as a capacity with which youth are endowed, as we have invoked by citing childhood studies literature and in our analysis of individual vignettes.

Childhood studies scholars embrace a concept of agency as a reaction against models of childhood with more structural and chronological substrates, allowing children to be recognized as meaning makers rather than passive recipients of action . However, in the present context, we must also see agency as a fundamental human process that is no less fundamental for being challenged by illness . Specifically, self-cutting is a crisis in the agentive relation between adolescent bodies and the surrounding world, or put another way, a crisis of their bodily being in the life-world that they inhabit. In understanding embodiment as an indeterminate methodological field, this relationship between body and world is defined by three modes or moments of agency: the intentionality of our bodies in acting on the world or being-toward-the-world, the reciprocal interplay of body and world embedded in a habitus, and the discursive power of the world upon our bodies to establish expectation and shape subjectivity . To be precise, approaching the interpretation of cutting from the standpoint of agency in these troubled adolescents’ body-world relationship has the immediate effect of shifting interpretive attention from the wounded flesh to the relation between the active hand of the cutter and the self-inflicted wound. It is then not just a matter of the pain, the relief, or the blood that originates at the violated boundary between self and world, and the concomitant breach in bodily integrity. In the first mode of agency, regardless of the implement used to cut with, the cutter’s hand is an agent of self, and the opening of the wound and flow of blood are an emanation of person hood into the world. Cutting is a form of active being toward-the-world whether understood as a form of projecting outward or as a kind of leaking and draining into the world. This mode of agency is epitomized in the statements of identity such as “I am a cutter.” In the second mode or moment of agency, hand and flesh together instantiate the reciprocal relationship of body and world. The cutting hand interpellates the part of the animal and material world that is one’s very own body, and that precise fragment of the world responds with the opening of the flesh . In this way cutting highlights the simultaneity of body as both self and other. The flow of blood marking not only the violation of a boundary but the opening between body and world. The reciprocity between body and world is highlighted in the simultaneous infliction of pain and the granting of relief.

The cutter’s body is also the locus of an anguished subjectivity that elicits the application to itself by an agentive hand ambivalently cruel and kind, of an otherwise inert implement from the material world,microgreen rack for sale whether it is a razor blade or a piece of glass. In the third mode of agency, both hand and flesh are no longer part of an inviolate self but conscripts of the world’s oppressive agency, and one’s body may as well not be one’s own but just a body, any body, “the” body as an object rather than a subject. The cutter’s hand is now the hand of the other, the wound is world-inflicted, and structural violence is incorporated at the most intimate bodily level. That is, it is inflicted by an anonymous oppressive world or the world dominated by the cruelty of others, and one’s flesh becomes an inert object alienated not only from selfhood but from the trajectory of a possible life, isolated from others and immersed in the immediacy of present pain and unproductive bodily transformation. We must take care to distinguish what is specific to each young person and what is fundamental to their bodily experience in the account we have just given. Attending to the immediate life worlds of individual youth reminds us that each has a distinct experience of cutting under distinct circumstances. Gender, ethnicity, and socioeconomic status matter to define these circumstances, while family relations and especially family instability are particularly insistent and frequent themes. Insofar as all the youth we have discussed were psychiatric inpatients, they can be counted among the more extreme instance of adolescent self-cutters, while exhibiting varied diagnostic profiles, levels of functioning, regimes of psychiatric medication, and phases of treatment and recovery. The combination of individual uniqueness and shared extremity across their situations has allowed us to elaborate a multilayered crisis of agency in the relation between body and world and highlights the existential profundity of cutting as a function of its mute immediacy in practice. The possibility for this kind of embodied existential analysis is that cutting is not an idiosyncratic occurrence but a culturally patterned act. Yet it cannot be accounted for just because other kids do it, and this is why it has been important to examine it in the lives of afflicted adolescents rather than simply as an element in the ethnography of “Emo” culture.

The interpretive point is that the trajectory of our argument from experiential specificity on the individual level to the fundamental human process of agency does not define the ends of a continuum. We must instead understand the extraordinary conditions of suffering as simultaneous with the enactment of fundamental human process, because the relation between body and world is always embedded in a specific instance, and each specific instance points to our shared existential condition of embodiment. Identifying the wounded flesh as locus of agency at the intersection of body and world as we have done brings to the fore a particular configuration of relations between self as active and passive, strategy and symptom, subjectivity and subjectivation. The moment of cutting is a fulcrum or hinge between the self as agent or as patient, with an intended pun on the medical sense of patient. From the standpoint of individual experience, cutting in the first sense is a strategy that is part of the self as agent, while in the second sense it is a symptom that is part of a disease process. As a cultural phenomenon, cutting in the first sense exhibits the body as existential ground of culture and wellspring of agentive subjectivity , while in the second sense cutting identifies the body as a site at which cultural practice and structural violence are inscribed and have the effect of subjectivation . In this respect, the distinction between subjectivation and subjectivity in the cut/cutting body is substantively parallel to the distinction between symptom and strategy in the afflicted person. Perhaps the analysis we have presented suggests that self-cutting may indeed be sufficiently complex to serve as the core of a distinct diagnostic category and too problematic with respect to agency to be defined as a symptom in the ordinary sense. Whether or not this proves to be the case, the existential complexity to which we have pointed is precisely what one would expect by bringing attention to bear on cutting as a crisis of agency with its locus at the intersection of body and world.Despite viral suppression on combination antiretroviral therapy , people with HIV suffer from depressed mood and chronic inflammation. Depression is the most common psychiatric comorbidity in HIV . Depressed PWH show poorer medication adherence , lower rates of viral suppression , greater polypharmacy , poorer quality of life and shorter survival . A sub-type of treatment-resistant depression in the general population is associated with chronic inflammation . The potential clinical significance of this is high, since the anti-inflammatory TNF-alpha blocker tocilizumab and other drugs such as the antibiotic minocycline, the interleukin 17 receptor antibody, brodalumab, and the monoclonal antibody, sirukumab, have been shown to be effective treatment for this depression subtype , but these have not been studied in the context of HIV. Inflammation is associated with greater symptom severity, differential response to treatment, and greater odds of hospitalization in patients with major depressive disorder.

The fourth factor was policy issues, referring to cases where the government or the facility itself does not allow for compliance with the signal functions. The fifth factor was designated as “no indication,” meaning that there was no patient group who needed this function. Supplemental Table 4 describes the reasons respondents provided on the survey for each unavailable signal function. Inappropriate supplies/equipment/drugs was the most common reason, as might be expected, and shortage of human resources was another causal factor. One intermediate hospital did not agree with the use of emergency signal functions for sentinel conditions, and answered “no indication” as their reason for non-compliance.It is widely recognized that there is a huge burden caused by trauma and non-communicable diseases in LMICs, where capability for emergency care is believed to be suboptimal.Many studies have tried to assess the state of emergency care in the health facilities of LMICs. Due to the accessibility issue, most studies examined teaching hospitals located in urban areas. Assessment tools were not standardized and were usually developed by the researchers themselves. Domains for assessment were usually related to the availability of resources, and functional aspects were surveyed with qualitative measures, if any. To our knowledge, this study is the first to survey urban and rural Myanmar hospitals using ECAT, the newly developed objective tool for assessing emergency care in health facilities. Our study demonstrated that the performance of emergency signal functions in Myanmar hospitals is inadequate, especially in trauma care. Trauma care in LMICs has been regarded as a role for large hospitals, and direct referral to upper-level facilities is a common practice. Burke et al. found that lack of readily accessible equipment for trauma care and shortage of skilled staff were the main reasons for poor quality trauma care in lower-level health facilities in LMICs.Another study pointed out the limited training opportunities for trauma management in LMICs.

We found similar obstacles to trauma care in Myanmar hospitals,flood and drain tray including the unavailability of items necessary for signal functions. Unlike other LMICs, Myanmar faces a singular geographic and demographic situation. Road conditions are poor. Almost 20 million people live in areas not connected by basic roads. The roads that do exist are unpaved and narrow, contributing to the overall lack of accessibility. The cause of this problem might be found in continuous armed conflicts. Since the independence of Myanmar in 1948, a continuing civil war has devastated the population and infrastructure of the rural areas, which has led to the deterioration of the health status of the country. In areas dominated by violence, residential zones are located away from road access, and the level of medical care is behind the times. Financial support is also lacking.For example, a referral and transport from Matupi Hospital to an adjacent upper-level facility takes as long as 16 hours during rainy seasons due to road damage . In this situation, timely management of patients in a critical condition is virtually impossible, and demands for higher levels of emergency care in basic-level facilities can be raised. Moreover, the results of our study show that some intermediate-level hospitals could not provide resuscitation for critical patients due to the lack of advanced airway management, mechanical ventilators, and defibrillation. Imbalances in the quality of emergency care in both basic- and intermediate-level facilities should be addressed carefully. However, in Myanmar’s special situation where highway infrastructure is lacking and there are problems with long transport times, the ability to administer emergency medical care at a large hospital should be established based on skilled labor and resources. Ouma et al. emphasized that all countries should reach the international benchmark of more than 80% of their populations living within a two-hour travel time to the nearest hospital.Although it cannot be realized in the near future, measures to alleviate accessibility problems can be applied.

Extension of critical signal functions for time-dependent conditions should be considered in selected basic-level facilities.In this regard, ECAT should be validated to include a time factor, such as the referral time to the nearest upper-level facility. We identified the following urgent issues in need of remediation: 1) improvement of trauma-related signal functions in basic-level facilities; 2) improvement of traumaand critical care-related signal functions in intermediate level facilities; and 3) implementation of a comprehensive nationwide survey to uncover emergency care deficiencies in rural areas, with emphasis on the time required for referral to higher-level facilities. Our suggestions to address the issues identified in our study can be summarized as relating to the reinforcement of infrastructure and human resources within each level of facility. In addition, prehospital care and care during inter-facility transportation should receive special attention considering the unique context of Myanmar, with its dispersed residences and extremely long transport times. There has been an effort to establish formal EM in Myanmar. In 2014, the Emergency Medicine Postgraduate Diploma course provided by Australia graduated 18 Myanmar medical officers.These emergency providers will be an imperative asset to setting up a modern emergency medical care delivery system in Myanmar, although most of them will practice in advanced-level facilities. Measures to build the capacity to respond to medical emergencies in rural areas should be pursued in Myanmar. There have already been efforts to improve first-aid skills among local healthcare workers who have a high degree of understanding of the local context, and to employ them as community emergency responders.These local healthcare workers are well informed about the population, hygiene, disease distribution, and the geographical and cultural characteristics of the area; thus, they are able to provide essential first aid and find appropriate health facilities for referrals. This practice has been expanded to the concept of out-of-hospital emergency care . It refers to a wide range of emergency treatments, from the process of recognizing an emergent care situation, to the initial emergency treatments outside the hospital, and transport to the hospital.

The establishment of OHEC has played a role particularly in LMICs by reducing mortality rates by 80%, especially in trauma cases.Since 2000, several organizations have implemented the trauma training course program with non-physician clinicians in Eastern Myanmar. The program comprises various skills for carrying out the initial treatment of trauma, taught through simple simulations and feedback. The findings indicated that survival rates improved significantly among major trauma patients following the implementation of this program. We recognize that some skills covered in the TTC, such as surgical airway management, would be relatively dangerous for health workers to perform in the field, and believe that development and implementation of a training program focused on the operation of emergency signal functions would be more practical for the rural context. Those who are trained in this program could act as prehospital emergency care providers, and also aid basic-level facilities to fill the functional gaps identified in this study. In addition to the above suggestions, a national or provincial strategic plan for reinforcing emergency care in rural areas of Myanmar should be established and implemented. Following a thorough investigational survey, essential resources for each level of health facility should be supplemented. Public education to recognize emergency conditions is another area to be strengthened. In many LMICs, including Myanmar, hydroponic tables canada folk remedies are still commonly attempted before people seek medical attention, especially in the field of obstetrics and gynecology.Recognizing the need for emergency care is crucial because it is the first step leading the patient to the emergency medical care system. Community education should play an important role in preventing delays in the detection of emergency situations.Traditional medicine providers have been the first to participate in this training thus far, and it has been reported to be effective.One limitation of the present study is the possibility of recall bias because we collected the data retrospectively. To minimize this bias, we selected five hospitals first, each of which had a key staff member whom we could contact frequently in a direct way. The other four hospitals were contacted via e-mail as a result of guidance we received from our initial five participants, who put us in direct contact with these additional research hospitals. Another limitation of our study is selection bias, given that the research hospitals taking part were not randomly selected. While the research hospitals were dispersed across various rural areas of Myanmar, they cannot be taken to represent each region,; however, they do provide a snapshot of the different levels of health facilities in Myanmar, and provide us with the basis for planning a more comprehensive survey on a larger scale in the future. Patients are commonly discharged from the emergency department without a pathological diagnosis to explain their symptoms, with one study finding that over one third of patients leave the ED with a symptom-based diagnosis .Studies exploring reasons for return ED visits have identified high levels of patient uncertainty related to lack of a definitive diagnosis as one cause for return.Introduction: Many patients who are discharged from the emergency department with a symptom-based discharge diagnosis have post-discharge challenges related to lack of a definitive discharge diagnosis and follow-up plan. There is no well-defined method for identifying patients with a SBD without individual chart review. We describe a method for automated identification of SBDs from ICD-10 codes using the Unified Medical Language System Metathesaurus. Methods: We mapped discharge diagnosis, with use of ICD-10 codes from a one-month period of ED discharges at an urban, academic ED to UMLS concepts and semantic types. Two physician reviewers independently manually identified all discharge diagnoses consistent with SBDs.

We calculated inter-rater reliability for manual review and the sensitivity and specificity for our automated process for identifying SBDs against this “gold standard.” Results: We identified 3642 ED discharges with 1382 unique discharge diagnoses that corresponded to 875 unique ICD-10 codes and 10 UMLS semantic types. Over one third of ED discharges were assigned codes that mapped to the “Sign or Symptom” semantic type. Inter-rater reliability for manual review of SBDs was very good . Sensitivity and specificity of our automated process for identifying encounters with SBDs were 84.7% and 96.3%, respectively. We describe a novel automated electronic approach using the UMLS to identify groups of patients who have been discharged from the ED with a SBD instead of a disease-specific diagnosis . Using manual physician review as the “gold standard,” we demonstrated a high sensitivity and specificity for the identification of SBDs using the UMLS semantic type of “Sign or Symptom.” The UMLS has been used in prior studies on ED EHR data for purposes including epidemiologic surveillance, constructing chief complaint dictionaries, and automated screening of rare conditions.These applications typically use UMLS with NLP, where free text is analyzed for concepts that were not otherwise captured in the EHR. Our work is different in that it was not intended for use with NLP or decision support, but rather was focused on automating the categorization of data fields that are not disease-specific for the purpose of identifying patients for research. Our recent work suggests that many patients discharged from the ED with a SBD have struggles related to their lack of a definitive diagnosis, with further work needed to explore the challenges unique to this patient population.3,4,16-18 Until now, there has not been a well-defined automated process for identifying these patients based upon their category of diagnosis instead of a specific diagnosis name . Our software was able to identify SBDs with a high sensitivity and specificity on the encounter level. False positives generally appeared to be pain or neurologic syndromes such as “seizure” and “musculoskeletal pain.” Some of these diagnoses are inherently ambiguous, as there are both primary conditions and secondary causes for many of these diagnoses. False negatives appear from predominantly three semantic types: “Finding,” “Disease or Syndrome” and “Pathologic Function.” Further refinement of our software may reduce the frequency of false negatives as we believe many of these diagnoses, such as “acute left ankle pain” or “vaginal discharge,” could also be described as a “Sign or Symptom.” However, it is important to note that the sensitivity of our analysis significantly improved when examining our results on the more clinically-relevant patient encounter level, as opposed to the diagnosis level.

Men and patients with Medicare or Medicaid insurance were more likely to have 14-day revisits, as were patients with a primary diagnosis of alcohol-related disorder; complication of device, implant or graft; congestive heart failure; and schizophrenia and other psychotic disorders. As a sensitivity analysis, we estimated the same model among adult patients only and found the results did not show any meaningful differences. Further, we repeated the analysis for each definition of frequent visitor definition and time horizons , and each combination of frequent visitor and time horizon. Skin and subcutaneous tissue infections were the strongest predictor of three-day revisits for each of the definitions of frequent visitor, followed by frequent visitor as the next largest association. In all other specifications, frequent visitor was the factor with the strongest association with revisits. There were 476,665 frequent visitors, who had a total of 1,251,082 visits, of which 340,381 were 14-day revisits. While frequent visitors represent 10.7% of all patients, they accounted for 18.7% of all encounters and 40.2% of all 14-day revisits. They were more likely to have a return visit at all times as compared to non-frequent visitors. Figure 2 demonstrates the percentage of patients revisiting the ED according to day after the index visit. The blue line represents all patients and shows that revisits peak on days one and two, and steadily decline thereafter, with slight peaks at days 7 and 14. The red line shows the revisit rate for patients with no or one visit in the six months prior to the index visit; as with all patients, the revisit rate peaks on days 1-2 and declines thereafter, dropping to below 0.3% by day 14. Patients defined as frequent visitors have revisits peaking on day 1 and decrease thereafter. The daily revisit rate for frequent visitors declines to a value of about 1.0% at 14 days,indoor grow cannabis after which the revisit percentage decreases by less than 0.1% for each subsequent day.

Encounters showing 0 days to first revisit reflect patients who returned to the ED on the same day as their index visit. Same day revisits represented 3.7% of the total encounters with an associated revisit. Frequent visitors had a significantly higher risk of a 14-day return visit resulting in admission than non-frequent visitors . Table 3 shows the unadjusted proportion of encounters resulting in return at 3 and 14 days according to different thresholds defining frequent visitor. For each threshold number of visits in the preceding six months, the unadjusted risk of return visit was more than double among frequent visitors as compared to non-frequent visitors. The remainder of the analysis uses two or more previous visits as the threshold defining frequent visitor, unless otherwise specified. This retrospective analysis of almost seven million patient visits found that recent previous ED visits was the strongest predictor of an ED return visit. This finding held true across multiple cutoffs defining frequent use, and also under both univariate analysis and a multivariate model including patient, visit, hospital, and county characteristics. Along with recent frequent use, public insurance and three diagnoses were associated with an increased risk of a return visit. This suggests that our understanding of short-term revisits could be informed by considering frequency of ED use.Previous studies have evaluated predictors of ED revisit using patient-level data such as age, sex, race, insurance status, and diagnosis at initial ED visit, as well as hospital-level data. Surprisingly, the relationship between frequent ED use and risk of revisit after discharge is poorly characterized.Further, there is no consensus on what defines “frequent,” with definitions ranging from 2–12 visits per year.We had the striking finding that even one previous visit increased risk of return by a clinically-significant margin. This finding held true even when accounting for patient, visit, hospital, and community characteristics.

Our definition focused on visits within the previous six months because other work has shown that episodes of frequent ED use are usually self-limited,42 which suggests that the recent past is more relevant to current health and risk of short-term return visit. A second, related finding is that the threshold used to define frequent visitors is arbitrary with respect to risk of return visit. In the hope of informing the wide range in the literature on the number of visits or length of time used to define frequent users,we considered our definition of frequent user in relation to risk of return visit. We had the surp finding that any number of previous visits used to define frequent vs non-frequent ED users predicted an increased risk of revisit. Given that the reason to label certain patients as frequent visitors is often in order to identify them for interventions, future work may consider an outcome-based definition of frequent users and define the term “frequent” with a qualifier – eg, with respect to propensity to revisit after a visit, risk of becoming a persistent frequent user, or risk of death. As with existing literature, we transformed the number of previous visits from a continuous variable to a binary one. This has the disadvantage of losing some information, but is standard in the literature regarding frequent ED use, and can easily be applied in the midst of clinical practice.Our sensitivity analysis demonstrated that any threshold was significantly associated with return visits, suggesting that knowing whether a patient had four vs three previous visits would provide marginally more information than simply knowing the patient had more than two previous ED visits. As with the definition of frequent user, the time to return visit defining a return visit is somewhat arbitrary. While the risk of return visit is highest on the first day following the ED visit, the risk gradually decreases and, as found previously by Rising et al., there is no clear timeline that defines a return visit.

This finding may suggest something other than inadequate care at the index visit is the driving factor for most short-term revisits, and that both frequent use and revisits may simply be proxies for certain patients with increased healthcare-seeking behavior. Further complicating this issue is that patients may be instructed to return to the ED for a re-evaluation. Thus, an ED in a setting with limited outpatient resources might appear to give poor care as measured by revisits when in fact it serves to provide followup care that patients otherwise would not obtain. Despite the variation in the literature and thus our broad range of models, we consistently found that the strongest predictor of a revisit is a high number of previous visits. This finding held true in our sensitivity analysis using different thresholds for number of previous visits and also days after index visit. The observation that previous visits predicts future visits may seem obvious or mechanical, but it does not necessarily follow that a patient with one or two visits in the prior six months would be at double the risk of a revisit within three days. Further,growing cannabis that this relationship was stronger than any other patient, hospital, or community characteristic is an important finding that has been overlooked in the literature regarding revisits. In fact, it appears that the literature on frequent visitors and the literature regarding revisits have to this point largely functioned in parallel and have not yet begun to inform each other. Whether frequent users are merely frequently-ill people, and whether sicker patients are at increased risk of short-term revisits deserves future research. Likewise, future work should investigate the extent to which patients are frequent users because they received poor care or face limitations in their ability to obtain outpatient resources, the extent to which revisits are avoidable, and the degree to which frequent use persists over time. Understanding the extent to which follow-up with primary care, referrals to specialists, and ability to obtain further evaluation such as advanced imaging, cardiac stress test, or even a wound check is essential to understanding why patients return to the ED. The data for this study were obtained from a single multi-state physician partnership and do not necessarily generalize to other providers or provider groups, or to other populations. However, the sample size was large and spans many cities and rural areas across several states, includes a broad set of hospital owner types, a large range of hospital sizes, and both teaching and non-teaching hospitals. This source of data may lead to a biased sample with respect to patient population, hospital characteristics, and provider characteristics. In particular, the income distribution is narrower than the distribution for the entire U.S., so the patient population could have a lower proportion of low- and high income patients than typical for the U.S. We addressed these potential sources of bias by controlling for patient demographics, patient insurance, and local income; hospital characteristics including volume and a performance metric, and clinician degree. Second, because not all hospitals within a region were observed, measures of frequent visitors and repeat visits may underestimate the actual numbers of frequent visitors and repeat visits, as patients may have gone to another ED either prior to or after the observed index visit.

This limitation is typical of this research,and in this dataset patients were linked across hospitals, although this was limited to the hospitals served by this company. Thus, it is unknown whether patients had an unobserved revisit at another ED, or whether what was considered an index visit actually represented a revisit after an initial visit at another ED. Next, we were unable to distinguish between planned and unplanned return visits. Thus, a patient who is instructed to return for a check over the weekend to ensure their illness is improving, for example, would appear to be a revisit, but this should not imply that their initial treatment was inadequate or inappropriate in any way. Research using administrative datasets, such as HCUP, likewise suffers from this limitation. Finally, as with related research, this study does not identify the extent to which high rates of frequent visits and revisits are driven by patient factors, ED care, or non-ED healthcare resources. This analysis was limited in its ability to examine patient psychosocial attributes or local resources, which are likely to contribute to ED visits and revisits, although we did consider proxies for access to care: patient insurance and community-level factors such as income and number of hospitals in the county. Acute heart failure is a gradual or rapid decompensation in heart failure requiring urgent management.The condition covers a large spectrum of disease, ranging from mild exacerbations with gradual increases in edema to cardiogenic shock. HF affects close to six million people in the United States and increases in prevalence with age.Currently, the emergency department initiates the evaluation and treatment of over 80% of patients with AHF in the U.S.As the population ages, increasing numbers of patients with HF will present to the ED for evaluation and management. However, making the correct diagnosis can be challenging due to the broad differential diagnosis associated with presenting symptoms and variations in patient presentations. Over one million patients are admitted for HF in the U.S. and Europe annually.In the U.S. population, people have a 20% risk of developing HF by 40 years of age.Patients with HF average at least two hospital admissions per year.Among patients who are admitted with AHF, over 80% have a prior history of HF, referred to as decompensated heart failure.De novo HF is marked by no previous history of HF combined with symptom appearance after an acute event.Mortality in patients with HF can be severe, with up to half of all patients dying within five years of disease diagnosis.Other studies have found that post-hospitalization mortality rates at 30 days, one year, and five years are 10.4%, 22%, and 42.3%, respectively.AHF expenditures approach $39 billion per year, which is expected to almost double by 2030.Normal cardiac physiology is dependent on appropriately functioning ventricular contraction, ventricular wall structural integrity, and valvular competence.At normal functional status, a person’s stroke volume is approximately one milliliter per kilogram for every heartbeat.SV is dependent upon the preload , after load , and contractility . In patients with HF, left ventricular dysfunction can be due to impaired LV contraction and ejection , impaired relaxation and filling , or a combination of both.

Even putting aside the questionable pharmacological and moral aspects of this differential policy, there is no evidence whatsoever for its effectiveness in controlling crime. Caulkins and colleagues show that conventional sentencing is significantly more cost effective. Although the crack mandatory sentences were trimmed somewhat in 2007, and the Supreme Court recently acted to restore some judicial discretion in these cases . Whether these changes will translate into a closing of the large racial differential remains to be seen. The optimal level of drug law enforcement is surely well above zero, but just as surely, well below current levels . Caulkins and Reuter argue that we could reduce the drug prisoner population by half without harmful consequences; they note that this would still leave us with system “a lot tougher than the Reagan administration ever was.” Kleiman suggests tactics for getting more mileage out of less punishment through the use of small, quick sanctions, strategically deployed. In 2005, there were about 1.8 million people in substance abuse treatment in the US, about 40 percent for alcohol, 17 percent for the opiates, 14 percent for cocaine, and 16 percent for marijuana . There are certainly many thousands of people who need treatment and are not receiving it. Whether expanding the available treatment capacity would bring them in is an open question. We should be wary of assuming that a purely “public health” approach to drugs can work; the police and courts play a crucial role in bringing people into treatment – increasingly so with the expansion of drug courts and initiatives like California’s Proposition 36, the 2001 law which permits treatment in lieu of incarceration for those convicted for the first or second time for nonviolent drug possession . For most primary drugs of abuse, criminal justice referrals are a major basis for treatment: in 2005, 57 percent of marijuana treatment, 49 percent of methamphetamine,indoor hydroponics cannabis and 27 percent of smoked cocaine. But 36 percent of clients in alcohol treatment were referred by the criminal justice system, so legal status may not be the crucial lever.

In a sophisticated cost-effectiveness analysis, Rydell and Everingham estimate that the U.S. could reduce cocaine consumption by 1 percent by investing $34 million in additional treatment funds, considerably cheaper than achieving the same outcome with domestic drug law enforcement , interdiction , or source country controls . But because treatment effects are usually estimated using pre-post change scores that are vulnerable to two potential biases . First, the post treatment reduction could reflect a simple “regression to the mean” in which an unusually extreme period of binge use would be followed by a return to the user’s more typical levels, even in the absence of treatment. Second, treatment pre- and post tests are vulnerable to selection biases because clients who enter and remain in treatment until post-treatment measurement are a non-random and perhaps very unrepresentative sample of all users. Regression artifacts would inflate treatment estimates; selection biases could either inflate or deflate the estimates. We believe that the full weight of the evidence makes it clear that treatment is both effective and cost-effective, but until these problems are better addressed, we cannot be sure that the benefits of expanded treatment would be as large as Rydell and Everingham implied. Even its most passionate advocates recognize that treatment’s benefits are often fleeting. About three quarters of heroin clients and half of cocaine clients have had one or more prior treatment episodes . Forty to sixty percent of all clients will eventually relapse, though relapse rates are at least as high for hypertension and asthma treatment . Importantly, Rydell and Everingham recognized that treatment can provide considerable health and public safety benefits even if it only reduces drug use while the client is enrolled. Held up to a standard of pure prevalence reduction , treatment is unimpressive. But by the standards of quantity reduction and harm reduction, treatment looks pretty good. American providers – steeped in the Twelve Step tradition – recoil at the phrase “harm reduction” – but it is a service that they can and often do perform quite well. Perhaps the most socially beneficial treatment modality is one that some are reluctant to view as treatment at all – methadone maintenance for heroin addicts. In 2006, there were 254,049 people receiving methadone, only about 20 to 25 percent of all opiate addicts in the US .

The gap is partly due to spotty service provision outside major cities, but in even urban centers, many addicts won’t voluntarily seek out methadone, preferring heroin even with its attendant risks. But Switzerland, the Netherlands, and Germany have amassed an impressive body of evidence that hard-core addicts significantly improve their health and reduce their criminality when they are able to obtain heroin directly from government clinics . Similar ideas were rejected in the US several decades ago, but perhaps it is time for a second look . In the US, the dominant form of prevention takes place in the classroom, generally administered by teachers . Ironically, prevention is the least well funded but most thoroughly tested drug intervention. Drug prevention has very modest effects on drug and alcohol use; e.g., the mean effect size in the most recent comprehensive meta-analysis was about 1/20th of a standard deviation . Considering that 1/5th of a standard deviation is usually considered the benchmark “small” effect size, this is not very encouraging. Making matters worse, the single most popular program, Drug Abuse Resistance Education , accounts for nearly a third of all school prevention programs , but numerous studies show it has little or no detectable effect on drug use . It is not clear whether its ineffectiveness stems from its curriculum or from its reliance on classroom visits by police officers. But classroom based prevention is quite inexpensive, so it doesn’t have to be very effective to be cost-effective. Caulkins and colleagues estimate over $800 in social benefits from an average student’s participation, for a cost of only $150. Most of the benefits involve tobacco prevention, then cocaine, and only minimally marijuana. Classroom-based prevention materials can’t be effective if the messages aren’t salient in real-world settings where drug taking opportunities occur. But a well-funded campaign of magazine, radio, and television ads by the Office of National Drug Control Policyc appears to have had no positive impact on levels of use . We should be wary of thinking we have evaluated “the impact of mass media”; it may just be that the messages we’ve been using aren’t very helpful. Note that our prevention messages are almost exclusively aimed at prevalence reduction rather than quantity reduction or harm reduction .

A greater emphasis on secondary prevention and harm reduction might have real payoffs with respect to social costs,pots for cannabis plants but we won’t know unless we try . Evidence from classroom sex education is instructive in this regard; programs that teach safe sex are reliably more effective at reducing risky behavior than are abstinence-based programs . We can hazard some guesses about where American drug policy might head in the future. The medical marijuana movement is likely to diminish in visibility as sprays like Sativex reduce the role of marijuana buyers’ clubs, yet adult support for marijuana legalization will continue to increase as the tumultuous “generation gap” of the 1960s becomes a distant memory. Methamphetamine will soon peak, if it hasn’t already , leaving us to deal with a costly aging cohort of addicts, much like our earlier heroin epidemic. And vaccines against nicotine and cocaine addiction may soon hit the market, with both desirable and unintended consequences . But rather than developing the case supporting these speculations, we close with two trends that are already well underway, each of which has the potential to seriously subvert current cultural assumptions about drugs and drug control. The conventional wisdom is that ecstasy is a “love drug” or “empathogen,” and that it is the drug of choice for European and Asian American college students and young professionals. But there are many reports of increased ecstasy use by minorities living in several cities . Many observers have noted its prevalence in the “hyphy” movement and the associated rap music . There is evidence of an increase in the number of references to ecstasy use in hip-hop music starting in 1996 . The reported rise in ecstasy use in the hip-hop scene has ignited alarming claims that ecstasy is “the new crack” ; a CBS television story asked whether Ecstasy was a “hug drug or thug drug” . In fact, researchers have only begun to examine the diffusion of ecstasy into inner-city neighborhoods . There is laboratory evidence of heightened aggression in the week following MDMA ingestion , but in a 2001 study of arrestees, ecstasy use was not associated with race, and negatively associated with arrest for violent crimes . It is also unclear whether self reported “ecstasy” use always involves MDMA, as opposed to closely related drugs like methamphetamine . Thus the emerging “thizzle” scene does raise intriguing questions about psychopharmacology, culture, and their intersection, but whether there is any meaningful causal connection between Ecstasy, race, and crime is far from certain. Earlier, we offered a thought experiment about a hypothetical drug called Rhapsadol. We now ask the reader to consider a newly created synthetic stimulant, “Quikaine.” Quikaine targets the neural system by increasing the speed of ion transfer between synaptic gaps. Thus, it reduces reaction time and increases the speed with which physical tasks can be accomplished.Neither does it affect intellectual functioning. Second, consider “Intellimine.” Its sole impact on the human body is to improve cognitive capacity; it has no other emotional or physical impact, and no lingering effect on mental functioning once the drug leaves the system. In addition, because variants of this drug have been used for decades to help with ADHD/ADD and Alzheimer’s it has a long and empirically sound safety record. In fact, children and the elderly receive maximum benefit of the drug. How should we regulate these drugs? Should they be legally available for purchase by adults? If not, are there more limited circumstances in which their use might acceptable? For example, would Quikane’s use be warranted by those charged with protecting others from danger, such as certain military operatives or police officers? What about for completing tasks faster and more safely, such as on an assembly line? How about for simply reducing the amount of time spent on household chores? Should we allow surgeons, crisis managers, and other high-stakes problem solvers to take Intellimine? These drugs are hypothetical, but new synthetics already have some of their properties, and there is every reason to expect rapid advances in the development of performance enhancers in the near future . They will raise vexing questions about personhood, agency, freedom, and virtue. For centuries, we have associated psychoactive substances with the pursuit of purely personal goals: fun, seduction, escape, transcendence, ecstasy. New drugs like Intellimine and Quikane will force us to come to grips with a radically new framing: Drug use as a tool for enhanced economic competitiveness. Parents who now worry about how marijuana might jeopardize their children’s Ivy League prospects may soon worry about whether abstinence lowers SAT scores. Employers who now screen urine for marijuana may come to view abstainers as slackers. It will be fascinating to see how we learn to reconcile these new pressures with our traditional attitudes toward drugs. We close with a brief list of topics that are sorely in need of research attention. Rather than a long wish list, we confine our attention to priorities that are implied by our analytical framework; specifically, the argument that quantity reduction and harm reduction deserve a more equal footing with prevalence reduction. The first priority is to give far greater attention to the development of quantity and harm indicators in epidemiological research. Our national drug surveys devote far more attention to prevalence than to dosage, settings of use, or consequences of use, and the reliance on household and classroom populations over represents casual users and under represents the heaviest users .

It should be appreciated that these adolescents are at high risk for future economic disengagement. It is not our intention to foster stigma or damage the prospects of NEET youth by adding the stereotype of ‘mentally ill’ to the stereotype of ‘unmotivated.’ Instead, our view is that treating their mental health problems early may be an intervention target with long-term dividends for the children themselves as well as society . Recent reports suggest that most British adolescents visit their GPs several times per year, which could provide opportunities to query mental health and substance abuse issues in primary care settings . However, the level of investment in child and adolescent mental health services in the United Kingdom is low and has further decreased in the face of the economic downturn ; moreover, coordination of care for young people transitioning out of adolescent mental health services into adult services is poor . Health service models that increase engagement and provide intensive employment support among economically inactive youths with mental health problems may be a more useful approach . There are limitations to our study. Our analysis was restricted to 18-year olds, a subset of the larger NEET population. We could not examine whether the associations between NEET status, self-perceived economic prospects, and mental health are similar among previous cohorts of young people. Our sample comprised twins, and whether their experience of NEET matches that of singletons is unknown. However, the NEET rate among our twins is similar to the official 12.5% rate reported by the UK Department for Education , and base rates of mental health problems in twins are very similar to population prevalence estimates . Our findings are also consistent with earlier work showing that NEET youths are much more likely to come from socioeconomically deprived families and neighbourhoods . The E-Risk study was not designed purposely to investigate NEET, as youth unemployment rose after the study began.

As a result, what is needed to grow marijuana we lacked information on how long participants have been NEET, and lacked the month to-month assessments needed to pin down sequential order between onset of 18-year-olds’ NEET status and changes in their mental status. Nevertheless, our prospective study waves revealed that some NEET youths’ mental health problems were of long standing. Additional methodological strengths of our study include its use of a representative birth cohort with good retention, and a comprehensive interview assessment of young people’s attitudes about work and their own economic abilities. The current high levels of youth unemployment in Europe and the United States are of grave concern. Policymakers and social welfare advocates continue to look for ways to improve the labour market outcomes of economically inactive young people . Our study contributes to this effort by highlighting the necessity of incorporating mental health services into youth career support initiatives. NEET youths are often assumed to be unwilling to work . Our analyses suggest, instead, that NEETs are as motivated as their peers, but many face longstanding psychological challenges that put them at a disadvantage when seeking employment. In an economic context that presents structural barriers to all would-be workers, NEET youths’ psychological vulnerabilities place them at even greater risk for a constellation of long-term socioeconomic perils.Electronic cigarettes and vaping products are new devices for inhaling various substances such as nicotine and cannabinoids, with or without flavoring chemicals. “Vaping,” or “Juuling,” is a term used to describe the use of e-cigarettes and vaping products.1 These devices, also known as e-cigs, vape pens, vapes, mods, pod-mods, tanks and electronic nicotine delivery systems, are available in different shapes and sizes.All e-cigarettes and vaping products are made of three components. The first component is the cartridge that contains e-liquid and the atomizer, a coil that heats and converts e-liquid into aerosols.

E-liquids can be broadly categorized into two types: regular e-liquids made of propylene glycolLoma Linda University, Department of Emergency Medicine, Loma Linda, California containing chemical flavors and vegetable glycerine used to dissolve nicotine or cannabis e-liquids containing tetrahydrocannabinol and cannabidiol. The second component is the sensor that activates the coil, and the third component is the battery.The hookah, also known as a water pipe, is an ancient method of smoking nicotine. In this method, the coal heats the tobacco and then the smoke passes through the water reservoir before it is inhaled.4 Contrary to public perception, hookah use is also associated with oral, lung, and esophageal cancers, similar to smoking cigarettes.4 In our study, we focused on e-cigarettes, and vaping, product-use associated lung injuries . According to the United States Centers for Disease Control and Prevention , in 2018 e-cigarettes were used by 3.05 million high school and 570,000 middle school students.EVALI is a diagnosis of exclusion, with a definition outlined by the CDC for confirmed and probable cases.6 EVALI was first identified in August 2019 after the Wisconsin Department of Health Services and the Illinois Department of Public Health received multiple reports of a pulmonary disease of unclear etiology, possibly associated with the use of e-cigarettes and related products.Since then, more than 2000 cases of EVALI have been reported, and in 80% tetrahydrocannabinol -containing products were used.Our study aimed to identify the clinical characteristics and hospital course of adolescents diagnosed with EVALI.We performed a retrospective chart review of adolescents presenting to our hospital between January– December 2019, with diagnosis of EVALI. Subjects were identified by the International Classification of Diseases, Tenth Revisiondiagnostic codes outlined by official ICD-10 guidelines.9The following codes were used: J68.0 ; J69.19 ; J80 ; J82 ; J84.114 ; J84.89 ; J68.9 ; T65.291 ; and T40.7X1 . We used a standardized data collection sheet. Data were collected by trained personnel who were not blinded to the objectives of study. The data extracted from the medical records were age, gender, weight, and vital signs obtained in the ED. We also compiled data on duration of symptoms, history of cough, shortness of breath, chest pain, vomiting, wheezing, rales, use of accessory muscles, and presence of altered mental status.

We also included data on respiratory support, duration of hospital stay, use of steroids during treatment, and laboratory tests and imaging obtained in the hospital and a negative infectious workup or the decision by the clinical care team to treat as a case of EVALI.Exclusion criteria were gastrointestinal and central nervous system manifestations without interstitial pulmonary involvement, ingestions of cannabinoids, duplicate visits, and if it was unclear whether vaping device was used or not. We used descriptive statistics to analyze the data. Median and interquartile range were calculated for continuous variables, and proportions were calculated with 95% confidence intervals for categorical variables. The study was approved by the Loma Linda University Institutional Review Board.We identified 16 encounters with the ICD-10 codes for EVALI during the one-year period. Using the exclusion criteria mentioned in the Methods section,heavy duty propagation trays we excluded seven patients. Four of these patients presented with CNS manifestations and vomiting without pulmonary involvement. In one patient, the history of vaping was unclear. One patient had ingested cannabinoids without vaping. Two encounters were excluded because they were duplicate visits. Of the seven patients included in the analysis, sixwere male. The median age was 16 years . The median weight in our series was 70 kilograms . The medians for vital signs recorded in the ED were the following: temperature of 100.2º Fahrenheit ; respiratory rate 24 breaths per minute ; oxygen saturation, 90% ; heart rate 130 beats per minute ; systolic blood pressure 128 millimeters of mercury; and diastolic blood pressure 76 mm HG . Three patients had documented fever in the ED. The most common symptoms reported in our study were cough, shortness of breath, and vomiting, each occurring separately in five patients. Three patients presented with chest pain. Two patients presented with altered mental status in the form of unresponsiveness, with one patient requiring intubation. The other unresponsive patient, a 16-year-old male, returned to a normal mentation with bag-valve-mask ventilation and naloxone but required high-flow nasal cannula for shortness of breath. On physical examination, accessory muscle use was the most common finding, reported in four patients. Rales were appreciated in two patients, while no patients were found to have wheezing . In our study, six patients presented with respiratory failure. Four required HFNC. One patient was intubated; one patient required simple nasal cannula oxygen at two liters per minute; and one patient maintained normal oxygen saturations in room air during his ED visit and was discharged home. A brief clinical presentation, summary of findings on imaging, and type of respiratory support needed are summarized in Table 2. Five patients were admitted to the pediatric intensive care unit, and one patient was admitted to the normal pediatric unit. The median hospital length of stay was six days . All patients were discharged with no comorbidities or deaths reported. Six patients were treated with steroids.Our patients had a variety of laboratory tests ordered. Most common were complete blood count, respiratory virus panel, respiratory cultures, and urine drug screen.

All patients had a complete blood count, and the median for white cell count was 16 thousand cells per cubic millimeter . A respiratory virus panel was collected from five patients and it was negative in all of them . Respiratory cultures were collected from two patients and both resulted negative. A urine drug screen was performed for six patients and was positive for cannabinoids in all six . Three patients followed up at different intervals in the pulmonology clinic . Spirometry showed normal results in all three patient sat that time. Case 1 followed up one week after discharge, at which time spirometry showed evidence of obstructive lung disease, which returned to normal at three-month follow-up visit. No repeat imaging was performed for that patient. Case 2 followed up six weeks after discharge with near-complete resolution of ground-glass appearance on repeat CT and normal spirometry. Case 4 followed up two weeks after discharge with improvement in lung opacities on repeat radiograph and normal spirometry. All three patients had received steroids for 10 days when they were originally diagnosed with EVALI. No follow-up data was available for the remaining four patients.EVALI was an emerging disease entity in 2019. In our case series, we describe adolescents diagnosed with EVALI and their clinical course in the ED and the hospital. In our study, the most common symptoms of cough, shortness of breath, and vomiting presented with an equal frequency of 71%. In a study by Layden et al, shortness of breath and cough was noticed in 85% of patients and vomiting in 61%; whereas, according to Belgaev et al, 90% of patients in their study presented with gastrointestinal and respiratory symptoms.In a report by the CDC, 85% of the EVALI population had respiratory symptoms and 57% had GI symptoms.11 The results of our study are similar to previous literature in suggesting that respiratory and GI symptoms are common in patients with EVALI. According to Balgaev et al, 67% of patients had clinical and radiological improvement with residual findings on radiological and pulmonary function tests at time of followup.In our study, the three patients who had documented follow-up visits had normal spirometry without residual deficits. Only two of those patients had repeat imaging, and both showed improvement without residual abnormalities. E-cigarette liquids and aerosols have been shown to contain a variety of chemical constituents including flavors that can be cytotoxic to human pulmonary fibroblasts and stem cells.Exposure to heavy metals such as chromium, nickel, and lead has also been reported.None of our patients were tested for heavy metal exposure. Most of the delivery systems have nicotine in them, with one cartridge providing the nicotine equivalent to a pack of cigarettes.In addition to nicotine, e-cigarette devices can be used to deliver THC-based oils.According to Trivers et al, one-third of the adolescents who used e-cigarettes had used cannabinoids in their e-cigarettes.In our patients with EVALI, urinary drug screen was positive for cannabinoids in all patients. One caveat is that we do not know whether our patients used only THC-containing products or a combination of nicotine and THC-containing products. In our case series, the majority of patients presented with pulmonary disease requiring respiratory support and intensive care unit admission. None of these patients developed acute respiratory distress syndrome .

The CAGE-AID has demonstrated validity, with high internal consistency in screening for problematic drug and alcohol use; a cutoff point of 2+ on the CAGE-AID has a sensitivity of 70% and specificity of 85% for identifying individuals with SUDs. Study exclusion criteria were current pregnancy, history of severe alcohol or drug-related medical problems , opioid overdose requiring Narcan , current opioid misuse without medication-assisted treatment, or attempted suicide within the past year. For this study, the target sample size was 50 participants; however, due to a high level of response and efficiency, enrollment was more than double our recruitment goal. Between March 27, 2020 and May 6, 2020, 3597 individuals were screened for study participation, with 3422 ineligible and 175 eligible individuals. Figure 1 shows the reasons for study exclusion, most frequently residing outside of the United States and endorsing fewer than 2 criteria on the CAGE-AID . Of the 175 eligible participants, 141 provided informed consent to participate in the study, of whom 128 completed the baseline survey.Among the 101 participants enrolled, 11reported previous use of the Woebot app. Described in detail previously, Woebot is an automated conversational agent that delivers CBT in the format of brief, daily text-based conversations. The Woebot program is deployed through its own native apps on both iPhone and Android smartphones or devices. The app on boarding process introduces the automated conversational agent, explains the intended use of the device, how data are treated,cannabis equipment and the limitations of the service .

The user experience is centered around mood tracking and goal-oriented, tailored conversations that can, depending on user input and choice, focus on CBT psycho education, application of psychotherapeutic skills for change , mindfulness exercises, gratitude journaling, and/or reflecting upon patterns and lessons already covered. Each interaction begins with a general inquiry about context and moodto ascertain affect in the moment. Additional therapeutic process-oriented features of Woebot include delivery of empathic responses with tailoring to users’ stated mood, goal setting with regular check-ins for maintaining accountability, a focus on motivation and engagement, and individualized weekly reports to foster reflection. Users become familiar with Woebot, which is a friendly, helpful character that is explicitly not a human or a therapist but rather a guided self-help coach. Daily push notifications prompt users to check in. We adapted W-SUDs, drawing upon motivational interviewing principles, mindfulness training, dialectical behavior therapy, and CBT for relapse prevention. Sample screenshots from the W-SUDs app are shown in Figure 2. In total, the W-SUDs intervention was developed as an 8-week program with tracking of mood, substance use craving, and pain, with over 50 psycho educational lessons and psychotherapeutic skills. CBT evidence-based, guided self-help treatments have ranged in length from 2 to 12 weeks, and the National Institutes for Clinical Excellence describes guided self-help as including 6 to 8 face-to-face sessions. Early responsiveness to SUD treatment is predictive of long-term outcomes, and brief addiction treatments are efficacious. Brief intervention can minimize potential dropout, a problem common to SUD treatment;therefore, we designed W-SUDs as an 8-week treatment. Woebot is not designed to address active suicidal ideation or overdose, and this was stated in the study informed consent. In addition, Woebot conversationally informs first-time users that it is not a crisis service. Woebot also has safety net detection that uses natural language processing algorithms to detect and flag several hundred possible harm-to-self phrases with 98% accuracy . Woebot detects crisis language and asks to confirm it with the user. If the user confirms, Woebot offers resources , carefully curated with expert consultation.

Woebot data indicate that users do not use Woebot for crisis management; approximately 6.3% trigger the safety net protocol, with 27% of those confirming that it is indeed a crisis when Woebot asks to confirm . W-SUDs, an automated conversational agent, was feasible to deliver, engaging, and acceptable and was associated with significant improvements pre- to post treatment in self-reported measures of substance use, confidence, craving, depression, and anxiety and in-app measures of craving. The W-SUDs app registration rate among those who completed the baseline survey was 78.9% , comparable with other successful mobile health interventions. As expected, the use of the W-SUDs app was highest early in treatment and declined over the 8 weeks. Study of engagement with digital health apps has been growing, with no consensus yet on ideal construct definitions. Simply reporting the number of messages or minutes spent on an app over time may undermine clarity and genuine understanding of the type and manifestation of app utilization related to clinical outcomes of interest. Further research in this area is warranted. The observed reductions from pre- to post treatment measures of depression and anxiety symptoms were consistent with a previous evaluation of Woebot conducted with college students self-identified as having symptoms of anxiety and depression. Furthermore, in this study, treatment-related reductions in depression and anxiety symptoms were associated with declines in problematic substance use. Declines in depressive symptoms observed from pre- to post treatment were greater among the participants in therapy. This study also examined working alliance, proposed to mediate clinical outcomes in traditional therapeutic settings. Traditionally, working alliance has been characterized as the cooperation and collaboration in the therapeutic relationship between the patient and the therapist. The role of working alliance in relationally based systems and digital therapeutics has been previously considered; the potential of alliance to mediate outcomes in Woebot should be further validated in future studies adequately powered to examine mediators of change.

Measures of physical pain did not change with the use of W-SUDs as reported in pre- and post treatment measures or within the app; however, the sample’s baseline ratings of pain intensity and pain interference were low. Although not a direct intervention target, pain was measured due to the potential for use of substances to self-treat physical pain and the possibility that pain may worsen if substance use was reduced,vertical grow shelf which was not observed here. Within-app lesson completion and content acceptability were high for the overall sample, although there was a wide range of use patterns. Most participants used all facets of the W-SUDs app: tracked their mood, cravings, and pain; completed on average over 7 psycho educational lessons; and used tools in the W-SUDs app. Only about half of the sample completed the post treatment assessment, with better retention among those screening higher on the CAGE-AID. That is, those with more severe substance use problems at the start of the study, and hence in greater need of the intervention, were more likely to complete the post treatment evaluation. None of the other measured variables distinguished those who did and did not complete the post treatment evaluation. This level of attrition is commensurate with other digital mental health solution trial attrition rates.By addressing problematic substance use, including but not limited to alcohol, the W-SUDs intervention supports and extends a growing body of literature on the use of automated conversational agents and other mobile apps to support behavioral health. A systematic review of mobile and web-based interventions targeting the reduction of problematic substance use found that most web-based interventions produced significant short-term improvements in at least one measure of problematic substance use. Mobile apps were less common than web-based interventions, with weaker evidence of efficacy and some indication of causing harm . However, mobile interventions can be efficacious. Electronic screening and brief intervention programs, which use mobile tools to screen for excessive alcohol use and deliver personalized feedback, have been found to effectively reduce alcohol consumption and alcohol-related problems. However, rigorous evaluation trials of digital interventions targeting non-alcohol substance use are limited. Furthermore, although a systematic review concluded that conversational agents showed preliminary efficacy in reducing psychological distress among adults with mental health concerns compared with inactive control conditions, this is the first published study of a conversational agent adapted for substance use. Study strengths include study enrollment being double the initial recruitment goal, reflecting interest in W-SUDs. Most participants reported lifetime psychiatric diagnoses, and approximately half of the participants endorsed current moderate-to-severe levels of depression or anxiety. W-SUDs was used on average twice per week during the 8-week program. From pre- to post treatment with W-SUDs, participants reported significant improvements in multiple measures of substance use and mood. The delivery modality of W-SUDs offered easy, immediate, and stigma-free access to emotional support and substance use recovery information, particularly relevant during a time of global physical distancing and sheltering in place.

More time spent at home, coupled with reduced access to in-person mental health care, may have increased enrollment and engagement with the app. Although further data on recruitment and enrollment are warranted, these early findings suggest that individuals with SUDs are indeed interested in obtaining support for this condition from a fully digitalized conversational agent. This study had a single-group design, and the outcomes were short term and limited to post treatment, thus limiting the strength of inferences that can be drawn. The sample was predominately female and identified as non-Hispanic White, and the majority were employed full-time. Non-Hispanic White participants reported higher program acceptability on 2 of the 4 measures compared with participants from other racial or ethnic groups. Future research on W-SUDs will use a randomized design, with longer follow-up, and focus on recruitment of a more diverse population to better inform racial or ethnic cultural programmatic tailoring, using quotas to ensure racial or ethnic diversity in sampling. Notably, although recruited from across the United States, nearly all participants were sheltering in place at the time of study enrollment due to the COVID-19 pandemic, which may have affected substance use patterns and mood as well as interest in a digital health intervention. Notably, however, alcohol sales in the United States increased during the COVID-19 pandemic. The primary outcomes of substance use, cravings, confidence, mood, and program acceptability were standard measures with demonstrated validity and reliability. The limitations were that all were self-reported, and acceptability measures were not open-ended or qualitative. Few participants were misusing opioids, likely due to study exclusion designed to mitigate risk, namely, the requirement of engagement with medication-assisted treatment and no history of opioid overdose requiring Narcan . Notably, nearly 1400 people with interest in a program for those with substance use concerns were excluded due to low severity on the CAGE-AID screener. Worth testing is the utility of digital health programs for early intervention on substance misuse that is sub-syndromal. Building upon the findings of this study, future research will evaluate W-SUDs in a randomized controlled trial with a more racially or ethnically diverse sample, balanced on sex and primary problematic substance of use; will employ greater strategies for study retention ; and will be conducted during a period with less restrictions on social contacts and physical mobility. Randomized controlled evaluations of conversational agent interventions relative to other treatment modalities are required. The COVID-19 pandemic, caused by the SARS-CoV-2 virus, took the world by surprise in early 2020 and resulted in unprecedented disruptions to normal life throughout the world as measures were put in place to control the spread of the deadly virus . Across North America, COVID-19 swept across the United States and Canada overwhelming health services and health infrastructure as cases exploded, hospitalizations exceeded capacity, and businesses and public programs like schools were forced to shut their doors, go online, or on hiatus . The physical and social impact was enormous – death rates grew exponentially and the healthcare system was pushed to exceed capacity in the face of enormous caseloads and a virus that spread rapidly . As schools, clinics, social venues, and otherwise non-essential businesses shut their doors, the most vulnerable in our society including those marginally housed, those experiencing substance use and/or those with mental health issues were even further marginalized as a result of lost services and support . Early in the pandemic, signs of increases in substance use raised concerns that substance use would skyrocket . Overdoses and particularly overdose deaths hit unprecedented levels and partially because of the reduced availability of emergency medical services .

Based on these findings, one could expect to find associations between perinatal hypoxia or severe OCs and hippocampal volume in the healthy controls as well, as we did in a previous study of schizophrenia patients and healthy controls. The hippocampus is, however, one of the brain regions in which neurogenesis occurs , and the number of hippocampal neurons , as well as the hippocampal volume as measured by MRI , might increase in response to different training tasks. On the other hand, hippocampal volume may be reduced in alcohol dependence and heavy cannabis use , as well as in several mental disorders including schizophrenia , unipolar depression and bipolar disorder , although we did not confirm the latter in this study. As such, a variety of factors may confound and interfere with putative associations between pre- and perinatal trauma and adult hippocampal volume. The number of possible known and unknown confounders not accounted for constitute one limitation in the current study. Although we did control for current lithium use, which is known to affect hippocampal and amygdala volumes in bipolar disorder, we did not have reliable data on cumulative medication use. Another possible limitation to the generalizability of the current study is the inclusion of patients across mood states, i.e. depression, mania/hypomania, and euthymia, since it has been suggested that amygdala volume may fluctuate across mood states. Third, the subject groups were relatively small when the bipolar disorder group was split into psychotic and non-psychotic subgroups, which may have caused type II errors within the statistical analyses. Finally, by studying severe OCs, and comparing subjects with them versus all other subjects , we placed high demands on the strength of the relationship, and may have missed possible associations between brain structure and less severe OCs. Strengths of the current study include the use of unbiased birth registry data, thorough clinical characterization of participating subjects, and the use of one MRI scanner with no upgrades during the study period. In summary,indoor garden table we report perinatal asphyxia to be related to smaller amygdala volume in patients with bipolar disorder. This suggests a neurodevelopmental component in the brain morphology of bipolar disorder.

The different associations between preand perinatal complications and brain morphology observed in patients with psychotic and non-psychotic bipolar disorder, as well as their possible functional consequences, warrant further investigation.Electronic nicotine delivery devices were developed as a less harmful source of nicotine to help cigarette smokers quit smoking. A recent large controlled clinical trial and epidemiological data support the idea that the use of e-cigarettes in smokers who are motivated to quit can promote quitting and are more acceptable than conventional nicotine replacement medications. However, the U.S. has experienced a recent surge of e-cigarette use among middle and high school students and young adults who are not using them to quit smoking. While most youth vaping is experimental as evidenced by less 10 days or fewer per month, a sizable fraction are vaping more frequently and some are become highly dependent on nicotine. Clearly, there is no health benefit for non-smokers who are using e-cigarettes. The question remains as to the nature and magnitude of adverse health consequences of nicotine vaping among non-smoking youth. To date, the main adverse effects that are documented in youth who vape nicotine are respiratory – cough and worsening of asthma. However, Faulcon and colleagues from the Center for Tobacco Products of the FDA, raise another worrisome health concern. These authors describe a series of 122 cases of seizures and other neurological symptoms associated with ecigarette use that were spontaneously reported to FDA or the American Association of Poison Centers between December 2010 and January 2019. The authors suggest that because of its known pro-convulsant effects, nicotine might be responsible for these events. The authors and the FDA appropriately request that healthcare providers assess the use of e-cigarettes in patients who present with seizures and submit reports to FDA when e-cigarettes are involved.However, the examination of the spontaneous reports, details of which are provided in the supplemental table, raises questions about a causal link, which needs to be considered in assessing the actual health threat of nicotine vaping for youth. A big question is why nicotine inhaled from e-cigarettes should cause seizures, while nicotine from conventional cigarettes does not. The intake of nicotine is typically similar to or lower from e-cigarettes compared to from tobacco cigarettes.

One needs to take in a very large dose of nicotine to cause seizures, and such an exposure would be expected to product other signs of nicotine intoxication. Also, toxicity after inhaling nicotine would be expected to occur quickly, as brain levels peak within minutes of inhalation, and would be expected to resolve within a few hours. As a first step in interpreting the association between neurological events, one needs to consider what the events actually were. Descriptions of the seizure events were provided by self-report, and are not always clear. In some case, tonic-clonic seizures are reported, but in other case shaking or seizure-like activity are reported. In most cases, records of a medical evaluation are not available. Nicotine can cause anxiety attacks and involuntary muscle contractions, but these are not seizures. Of note is that in 54 cases the reporters continued to vape nicotine after the first event, and had recurrent seizure events. Continued use would be surprising if the user had previously experienced a real seizure. The probability of causation can be analyzed by considering three elements: 1) biological plausibility; 2) timing of the event in relation to the dosing of the product; 3) the presence of alternative explanations. Biological plausibility. With respect to biological plausibility, as mentioned above, a nicotine overdose can cause seizures, and nicotine can cause seizures in some animal models of epilepsy. Seizures have been observed in adults who were poisoned with nicotine, and in young children who have consumed liquid nicotine, including nicotine-containing e-liquids. Severe nicotine poisoning is expected to cause nausea, vomiting, pallor, sweating, abdominal pain, salivation, lacrimation, muscle weakness, confusion and lethargy before one experiences seizures. These symptoms have been reported of oral or dermal exposure; it is possible that inhalation of a high dose of nicotine may produce a different syndrome, but it seems unlikely that seizures would appear without other manifestations of systemic toxicity. While nicotine overdose can cause seizures, lower doses of nicotine may have anticonvulsant activity in people. An anticonvulsant effect of transdermal nicotine has been reported in people with autosomal dominant nocturnal frontal epilepsy and in focal epilepsy. 

Cigarette smoking per se is associated with an increased risk of seizures, but this appears to be due to medical complications of smoking rather than acute effects of nicotine. Another biological plausibility issue relates to several spontaneous reports of recurrent seizures in the absence of vaping. As mentioned before,microgreens grow rack the effects of nicotine are relatively brief, and cannot explain recurrent seizures at a later time. Most likely, these individuals have a seizure disorder. Whether nicotine can trigger a seizure in a person with an underlying seizure disorder is unclear. Timing of events. The timing of seizures in relation to vaping in the series was quite variable. 62% had a seizure within 30 minutes and a few had seizures immediately after vaping. If inhaled nicotine caused seizures, seizures would be expected to occur within minutes of vaping, when brain levels are highest; however, many of the seizure cases reported a much longer time lag. In eight cases, a seizure was reported after first use, and in some cases after a single puff. Generally, a novice vaper inhales the e-cigarette aerosol inefficiently and is exposed to less nicotine than an experienced vaper and takes in less nicotine than a person gets from smoking a cigarette. It is hard to imagine that the dose of nicotine in a single puff would be sufficient to cause a seizure. Alternative explanations. Many of the case reports suggested alternative explanations for seizures. Some had known seizure disorders, some used cannabis and other drugs in addition to nicotine. Some vaping liquids have been reported to be adulterated with synthetic cannabinoids, cocaine and/or caffeine, all of which can produce seizures. Could a chemical other than nicotine be the cause of seizures with e-cigarette use? The typical e-liquid contains nicotine, propylene glycol, glycerin and flavoring chemicals. Propylene glycol and glycerin are not known to cause seizures, although at high heating temperatures they may be degraded to form toxic chemicals such as formaldehyde, acetaldehyde and acrolein. The amount of these chemicals are however usually lower than those found in cigarette smoke, and cigarette smoking does not acutely cause seizures. Some flavoring chemicals are cytotoxic, but there are no reports of these chemicals causing seizures. Analysis of the case reports in the paper by Faulcon raises many questions about the nature of the seizures and other events, and whether there is a causal link to nicotine vaping. A formal causation analysis, which has not yet been done, would likely indicate possible causation at most. At this point in time I would not consider seizures to be a potential adverse effect that should influence the decision of an adult smoker to use e-cigarettes to try to stop smoking conventional cigarettes.However, the possibility of neurological events reported by young vapers should not be ignored.

The U.S. is currently experiencing an outbreak of cases of acute lung injury in young people from vaping illicit cannabis products and possibly some adulterated nicotine liquids. Similar to the guidance given to healthcare providers regarding acute lung injury, providers should be aware of a possible link between nicotine vaping and neurological events, should carefully evaluate medical causes of such events, including detailed neurological evaluation and biochemical screens for illicit drug use, should collect vaping devices and liquids for later analysis if possible, and should report such cases to the FDA and state health departments. Of course, the best solution to address the concern about seizures from e-cigarette use is to eliminate vaping by non-smoking youth. Some public health authorities and politicians have urged banning the sale of e-cigarettes completely to reduce e-cigarette use in youth. The public health cost of such a policy would be to deny adult smokers the availability of a cessation aid that may be life-saving.Policies of banning sales of e-cigarettes in gas stations and convenience stores, but allowing sale in specialty tobacco and vape shops, and over the internet, where age verification of purchases can be enforced, are reasonable. Hopefully, in this way youth can be protected from harm while supporting the potential benefits of ENDS in reducing the devastating harms from smoking in adults. The US is in the midst of a staggering opioid overdose crisis with 47,600 of 70,237 total drug overdose deaths involving opioids in 2017. The “Triple Wave” opioid epidemic began with a rise in prescription opioid deaths in the 2000s, followed by a sharper rise in heroin deaths, and then in the last few years, a rapid rise in synthetic opioid deaths, cresting over the prior two waves. The reformulation of OxyContin to the abuse-deterrent OxyNEO in 2010 likely caused a large demand shift from prescription opioids to heroin. Starting in 2004, states began implementing electronic prescription drug monitoring programs with varying enforcement levels, further reducing the availability of prescription opioids and causing a further shift towards heroin. Heroin prices had been low since the 1990s after Colombian-sourced heroin entered the US market , making heroin a readily available and inexpensive substitute for many opioid consumers despite the stigma. Among large parts of the eastern US, the illicit opioid market has transitioned from primarily consisting of heroin and black market prescription opioids to products marketed as heroin or black market prescription opioids, but which in fact are adulterated with or substituted by illicitly produced synthetic opioids: fentanyl, fentanyl analogs such as carfentanil, and other synthetic opioids such as U-47700. Historically, there have been limited spikes in overdose deaths due to the substitution of heroin with fentanyl. The earliest known example in the US was a spike in overdose deaths in California in 1979 with the introduction of so-called “China White”, later determined to be 3-methylfentanyl. 

The substance use dependent behavior variables are constructed from adolescents’ self-reports of their smoking, drinking, and marijuana use levels. We define the smoking, drinking, and marijuana use response category levels based on four considerations: the statistical distribution of each substance use behavior among US adolescent in the mid-1990s, how each substance use behavior question has been asked in the Add Health survey, assuring that there are not too few observations for statistical reasons at a particular value, and the approach utilized in previous studies, including Pearson et al. and Mathys et al..A methodological challenge we face is that whereas the questions about smoking and drinking behavior were asked at all three waves, questions about marijuana use were only asked at t2 and t3. One approach would discard all the information at t1 , but this strategy will reduce the efficiency of analysis, increase standard errors, and decrease statistical power. Instead, we reconstruct adolescent marijuana use at t1 based on four questions. Fig 2 provides a flow chart of the logic, and shows that we in fact have a considerable amount of information that can help us reconstruct probable values for the vast majority of the adolescents. First, if an adolescent has never tried marijuana at t2 , s/he would not have used it at t1, so we can safely code them as a zero at t1. Next, if an adolescent has tried marijuana at t2 but the age at which he or she tried was above his or her age at t1 , s/he would not have reported using it at t1, so we can safely code them as a zero at t1. Finally, if an adolescent has tried marijuana at t2 and the age of usage was below his or her age at t1 , we utilize information from two questions “During your life, how many times have you used marijuana?” and “During the past 30 days, how many times did you use marijuana?” at t2. In a few instances the difference between these two variables is zero,grow rack which appears to be a reporting error as they reported all their usage in the last 30 days and yet that they started at a young age.

We code them as a zero at t1 under the presumption that this earlier usage was very limited, and perhaps experimental. However, if the difference is non-zero, since the In-School Survey was conducted at least six months before the wave-1 In-Home Survey, we divide this difference by 5 to average over five months [i.e., /5]. Those with values less than 1 were categorized as non-users at t1 , those with values between 1 and 10 were categorized as light users and those with values above 10 were categorized as heavy users. Light users comprised about 16% of adolescents in Sunshine High and 17% of adolescents in Jefferson High. Likewise, heavy users comprised about 5% of the adolescents in Sunshine High and 8% of the adolescents in Jefferson High. Overall, this reconstruction strategy enabled us to estimate a three-wave SAB model for each of the two samples without discarding any data. The last step of the reconstruction procedure for the heavy marijuana users is not perfectly accurate and might mistakenly categorize a few light users as heavy users, since they could have used marijuana outside of the last five months. The proportion of cases that might have been mis-classified is less than 10%. Furthermore, sensitivity tests in which the level of marijuana use for these uncertain cases was randomly assigned to “light” or “heavy” use exhibited similar results over a large number of samples.As shown in Table 2, our estimated SAB model includes a smoking behavior equation, a drinking behavior equation, a marijuana use equation, and a network equation. Based on the smoking behavior equation, those who were one point higher on the marijuana scale are 25% [exp = 1.25] and 15% [exp = 1.15] more likely to increase their own smoking behavior at the next time point in Sunshine High and Jefferson High, respectively. Those who drank alcohol did not smoke more over time. There is no evidence of cross substance influence, as having more friends who drank or used marijuana did not impact a respondent’s own smoking over time. In ancillary models, we measured average level of drinking or marijuana use for friends and these effects were also statistically insignificant. These results are shown in S1 Table. Regarding the other measures in the smoking behavior equation, we detect a negative smoking behavior linear shape parameter in both school samples along with a positive smoking behavior quadratic shape parameter.

This suggests that adolescents were inclined to adopt lower levels of smoking behavior over time, but they also tended to stay as or become non-smokers or escalate to heavy-drinkers due to a pull towards extreme values of this scale. Turning to the peer influence effect, we find that adolescents’ own smoking levels were affected by that of their best friends in both schools. There is no evidence that parental support or monitoring reduced levels of smoking over time in either sample. African Americans and Latinos smoked less than Whites in Sunshine High. Depressive symptoms were found to increase smoking behavior in Jefferson High. In the drinking behavior equation, we find that an adolescent who was one point higher on the marijuana use measure was 22% and 16% more likely to increase their own alcohol use at the next time point in Sunshine High and Jefferson High, respectively. However, respondents’ drinking was not related to their greater cigarette use. There is no evidence that friends’ smoking behavior or marijuana use affected respondents’ drinking behavior. This was the case whether measured as the number of friends who smoked or used marijuana, or as the average level of such behaviors. A negative linear shape effect and a positive quadratic shape effect are also confirmed regarding drinking behavior. An adolescents’ drinking level was positively predicted by that of one’s best friends. Whereas there is no evidence in these two networks that high levels of parental support impacted drinking levels of adolescents, we do see that higher levels of parental monitoring were associated with lower levels of drinking behavior over time in Jefferson High. In Sunshine High, African Americans were found to drink less than Whites, and depressive symptoms were found to increase drinking levels. The marijuana use equation suggests no evidence that increasing usage of the other two substances leads to increasing marijuana use. We once again see no evidence of cross-substance influence, microgreens shelving as the number of friends who smoked or drank or the average smoking or drinking level of friends is not related to ego’s marijuana use levels over time. A negative linear shape effect and a positive quadratic shape effect are also detected on marijuana use behavior. Across both samples there is very strong evidence of a peer influence effect from anadolescent’s best friends’ marijuana use to an individual’s own marijuana use.

Higher levels of parental support or monitoring were not found to reduce levels of marijuana use over time. For all three substance use behaviors, there was no evidence that adolescents who are more “popular” were any more likely to increase their substance use over time. In the network equation the expected patterns are detected regarding the endogenous network structural effects across samples. At the dyadic level, adolescents did not randomly nominate peers as friends, since friendship ties inherently require the investment of time and energy, as indicated by the negative out-degree parameters; instead, adolescents tended to nominate peers who had already nominated them as friends previously, as indicated by the positive reciprocity parameters. At the triadic level, adolescents tended to nominate a friend’s friend as a friend but avoided ending in 3-person cyclic relationships. The negative out-degree/in-degree popularity parameters and the out-out degree assortativity parameters suggest that adolescents were less likely to befriend peers who have already made/received many friendship nominations or have similar out-degrees. Instead, they were more likely to befriend peers with similar in-degrees, as indicated by the positive in-in degree assortativity parameters. We also find that adolescents were more likely to nominate peers as friends if they were of the same gender, race , and grade. Grade is a particularly strong effect, as adolescents were 86% and 77% more likely to nominate a friend if they were in the same grade than if they were in a different grade in Sunshine High and Jefferson High, respectively. Lastly, the limited nomination parameter shows that for adolescents who encountered the administrative error of being limited to nominate only one male or one female friend, their odds of nominating friends is re-adjusted by the SAB models to be 132% larger in Sunshine High and 297% larger in Jefferson High than those with no such problem.Whereas our initial models tested the relationship between interdependent substance use behavior, they assumed that these effects are symmetric: that is, usage of one substance equally increases or decreases usage of another substance. In our next set of models, we relax this assumption and test whether usage of one substance increases behavior of another substance or decreases behavior , or both. These models were estimated separately as the combined model exhibited extreme collinearity. As shown in Table 3, there is a significantly positive creation function from marijuana use to drinking in both samples, implying that respondents’ marijuana use increased their odds of drinking initiation. Thus, one unit higher marijuana use made a nondrinker 62% and 60% more likely to start drinking rather than stay as a non-drinker at the next time point in Sunshine High and Jefferson High, respectively. On the other hand, the endowment function from marijuana use to drinking is not statistically significant at either school, implying that marijuana use does not affect the likelihood of stopping drinking behavior.

We detect a statistically significant creation function in Sunshine High: a one unit increase in marijuana use increases the odds 62% that adolescent non-smoker will initiate smoking rather than stay as a non-smoker. There was no evidence of a statistically significant endowment function in Sunshine High. On the other hand, the pattern is reversed in Jefferson High with a statistically significant endowment function but a statistically insignificant creation function. Thus, in Jefferson High although marijuana use does not impact respondent’s likelihood of smoking initiation, one unit higher marijuana use made smokers 27% more likely to stay as smokers rather than quit smoking at the next time point.To understand the magnitude of these effects , we engaged in a small simulation study in which we omitted some of the effects from the SAB model shown in Table 2 and assessed the consequences for the level of substance use behavior in the schools. That is, we changed a particular parameter value from the one estimated in the model to zero, and then simulated the networks and behaviors forward 1000 times. We then assessed the average level of smoking, drinking, and marijuana use in the network at the end of the simulation runs. To save space, we only present the results for Sunshine High; see S2 File for the Jefferson High results, which were similar.The highest level of smoking is observed when we set to zero the influence effect of friends on smoking behavior, as the percentage of non-smokers drops from 72% in the original model to 63%, and the percentage of heavy-smokers increases from 11% to 18%. The pattern was similar in Jefferson High, with analogous values of 48% to 42%, and 31% to 35%. This corroborates the findings in previous simulation research that peer influence has a protective effect on smoking and drinking adoption. The lowest levels of smoking are observed in the hypothetical scenario in which marijuana use has no effect on one’s own smoking behavior, as the percentage of non-smokers rises from 72% to 81%, and the percentage of heavy-smokers decreases from 11% to 5%. The analogous values in Jefferson High were 48% to 54%, and 31% to 25%. Regarding drinking behavior, we see that the effect of one’s own marijuana use is particularly important as setting this effect to zero results in a decrease in drinking behavior. 

Participants were interviewed via video or audio call except in one case, where responses were collected by e-mail. With permission, calls were recorded and transcribed.The analysis began with calculation of descriptive statistics, including the percentage of pharmacies that furnished naloxone identified in the telephone survey. For interviews with the subset of naloxone furnishing pharmacists, descriptive analysis summarized the extent of furnishing for medications other than naloxone. Transcripts of each interview conducted, as well e-mail responses, were uploaded to Atlas.ti software for qualitative data analysis and deidentified by numbering each interview. Beginning with codes developed from past research on furnishing practices as a preliminary guide, as well as inductive methods to identify potential novel concepts, the investigators developed a code book classifying statements as referring to barriers or facilitators, then further subdivided them by type in Atlas.ti. Complete sentences were the minimum unit of analysis coded in the transcripts to identify common themes.To ensure validity and consistency across interviews and coding, each interview was conducted by a minimum of 2 researchers, and coding was completed simultaneously by all of the researchers who had conducted interviews. Disagreements were resolved by discussion until the group reached consensus. Transcripts, findings, and key quotations used to illustrate them were summarized in drafts circulated to the entire research team. Findings were triangulated based on reviews of previous studies of furnishing. Only findings identified as relevant by the group were included in the final analysis.The second step of data collection was interviewing furnishing pharmacists in the region for interviews about barriers and facilitators to furnishing. Among the contacted pharmacies that furnished naloxone, 8 furnishing pharmacists agreed to be interviewed.

The stores where these pharmacists worked represented 5 of the 11 counties in the Central Valley. Of these, 5 were associated with a chain pharmacy,microgreen flood table while the remaining 3 were independent. Although previous research on furnishing rates is limited, it suggests that naloxone furnishing is more common than furnishing of other medications.Interview participants were asked whether they also furnished other medications; as some of the factors that discourage or encourage furnishing may be consistent across medications. Six respondents indicated that the stores where they worked also furnished hormonal contraception, 3 respondents that their stores also furnished nicotine replacement therapy , and 1 that their store also furnished preexposure prophylaxis/post exposure prophylaxis. Respondents indicated that the pharmacies where they worked filled between 250 and 1000 prescriptions per day, averaging approximately 500. The time that respondents had held their positions ranged from 5 months to 20 years, and none had completed a residency. Results are provided in Table 2. With respect to barriers to furnishing, all interview participants listed cost to patients as the primary barrier. They noted that insurance did not necessarily cover naloxone, and when it did not, patients would not purchase it. As one stated, “The biggest barrier to this is first of all money. If it’s zero copay, they probably will take it. If there’s any copay, they’re just normally not going to pay for it.”. Other barriers to furnishing included time, cost, stigma, and lack of a shared language. Reported heavy workloads and a lack of dedicated time to integrate naloxone screening into the pharmacy workflow was cited by 6 of 8 respondents as making it difficult to prioritize furnishing naloxone. One respondent noted, “It’s really time. We don’t really have time here to initiate for those implementing naloxone […] unless patients request it.”. With respect to stigma, 5 respondents stated that it was difficult to suggest supplying naloxone to patients due to its association with drug abuse. They indicated that patients perceived offers of naloxone as accusations of opioid abuse. One stated, “[T]here’s always like that lash back from a patient, like oh, I don’t need it because I’m not abusing it. That’s the common phrase.”

Lastly, one respondent reported that the absence of a shared language was a barrier due to lack of understanding and miscommunication, noting that, “[W]e have to get a translator to […] communicate with the patients. Maybe the patient’s not understanding correctly even [as] it’s being translated.”. Examples of responses regarding barriers to furnishing are shown in Table 3. Although California Assembly Bill No. 2760, which passed in 2018, required medical prescribers to offer a naloxone or equivalent prescription to populations at higher risk of opioid overdose, out-of-pocket costs to the uninsured in the United rose 500 percent from 2014 to 2018 for certain brands of naloxone.Generic naloxone has an average wholesale price of $64.80-$75.00.Participants believed that reducing out-of-pocket costs could increase naloxone purchase and use. A chain community pharmacist stated that they went “out of their way to try to find GoodRx discount cards to help bring down the price for patients.” and that doing so reduced patient reluctance to purchase naloxone. Similarly, an independent community pharmacist suggested that “lower [ing] restrictions and mak[ing] it OTC [over the counter]” would increase the likelihood of visitors purchasing naloxone. Participants were also asked to identify facilitators to furnishing. Responses included collaborating with other health professionals, closer proximity to pain clinics, expanded scope of pharmacy practice in California, supportive corporate policies, education and training on naloxone furnishing, and higher demand for naloxone. With respect to collaboration, 2 respondents stated that closer proximity to pain clinics increased the likelihood of pharmacies furnishing naloxone. One pharmacist stated that, “some pharmacies are located in regions [with] higher potential [of] abuse …that can also drive up having … more Naloxone in that location.”. One pharmacist indicated that demand was higher in their region, stating that, “people started asking for it. We dispensed it”. Additional examples of responses regarding facilitators to furnishing are provided in Table 4.Since 2013, California has sought to expand access to care by authorizing pharmacists to furnish medications.

Implementing naloxone furnishing by pharmacists in particular provides a potential opportunity to reduce opioid overdoses. These services are especially critical in rural areas like California’s Central Valley that have been disproportionately impacted by the opioid epidemic.We were unable to identify any prior studies that assessed the extent of pharmacist furnishing in rural, HPSAs such as the Central Valley, and our findings suggest that contrary to initial expectations, almost half of contacted pharmacies, including some mail-order pharmacies, furnished naloxone in the Central Valley. In contrast, a study of primarily urban pharmacies in California conducted in 2020 found that 42.4% furnished naloxone.Interviews with pharmacists who furnished naloxone suggested that pharmacies continued to face barriers to successful implementation,seedling grow rack many of which have been identified in previous research. These included time restrictions, high outof-pocket costs for purchasers, stigma associated with opioid use, and in 1 case, language barriers. All respondents indicated that out-of-pocket costs were the most critical barrier and that prices varied depending on insurance coverage; this finding is consistent with prior research.The findings regarding stigma as a barrier to offering and accepting naloxone are also consistent with previous research. This includes a study involving pharmacy students in Tennessee and their perceptions of naloxone use and opioid use disorder patients, which found that although pharmacy students are capable of and predisposed to furnish naloxone, successful furnishing is complicated by limited patient awareness and stigma, specifically the perception that naloxone is for “addicts” only.Another study examining undergraduates’ reactions to fictional vignettes about people with opioid use disorder found addiction was attributed to the opioid user’s character and varied by an user’s socioeconomic status.Studies examining perceptions of take-home naloxone conducted with both healthcare providers and opioid users have found that stigma influences both parties when providing education and seeking out information about naloxone and overdose prevention, respectively.These studies suggest that further interventions in pharmacy education to combat stigma against naloxone use and opioid use disorder might help facilitate increasing naloxone furnishing rates.Limitations to this study include generalizability, variable effects of coronavirus disease 2019, and self-reporting bias. The analysis only considered the 11 counties in the Central Valley, which may limit extrapolation outside of this region. The sample also did not include interview data from pharmacies that furnished but chose not to participate, which may have resulted in a biased sample. Another limitation is that this study was conducted 2 years after the most recent comparison study of naloxone furnishing in California. As a result, the higher furnishing rates observed in this study may have re- flected a time trend or effect of the coronavirus disease 2019 pandemic, such as difficulty securing appointments with physicians encouraging use of pharmacy services, rather than a difference in prevalence.

Interview data were self-reported and may have reflected social desirability bias or human error. One interview was done through e-mail, rather than a phone call, which limited the ability to probe for clarification and additional detail. Pharmacies that did not furnish naloxone were not included in interviews on the grounds that they would be unable to provide information on facilitators to naloxone furnishing; future studies could investigate if these pharmacies furnish other medications. Additional research could also address potential differences in furnishing practices between independent and chain pharmacies, as well as furnishing rates for other medications in this region. Irrespective of these limitations, the findings provide new information regarding pharmacist furnishing in HPSAs, barriers that prevent the widespread provision of naloxone, and potential strategies that may help overcome those barriers.Discrimination against LGBTQ+2 people has a significant impact on economic equity. LGBTQ+ people face higher rates of poverty than non-LGBTQ+ people, especially transgender and bisexual people, LGBTQ+ people of color, and those living in rural areas.3 Unions have aligned with LGBTQ+ advocacy groups to fight for legislation prohibiting discrimination in employment on the basis of sexual orientation and gender identity. In Canada, protections against discrimination in employment were recognized nationally under Section 15 of the Canadian Charter of Rights and Freedoms in 1995 and were then codified by the Canadian Human Rights Act in 1996 and 2017.4 In the US, 21 states and the District of Columbia have explicit legislative protections against discrimination based on sexual orientation and gender identity in employment, housing, and public accommodations.5 As of June 2020, protections from discrimination based on sexual orientation and gender identity were upheld by the Supreme Court as implicit in Title VII of the Civil Rights Act of 1964.6 Despite these recent gains, the fight for LGBTQ+ equity and social justice is far from over.Even in regions with long-standing nondiscrimination protections under the law, LGBTQ+ people continue to experience stigma and mistreatment on the job.8LGBTQ+ people are an increasingly organized portion of the United States and Canadian workforce. LGBTQ+ union members and their allies in both countries have mobilized to form coalitions and constituency groups to integrate civil rights protections into their union constitutions, contracts, collective bargaining agreements, and economic justice campaigns. The United Food and Commercial Workers union has joined broader labor organizing and solidarity movements to fight for the rights, safety, and dignity of LGBTQ+ union members and their families in Canada and the United States, mobilizing to form coalitions and constituency groups to integrate civil rights protections into their union constitutions, contracts, collective bargaining, and economic justice campaigns.Over the past three decades, LGBTQ+ union activists and leaders have won considerable gains within their local and international unions, including the successful formation of UFCW OUTreach as a recognized constituency group in 2013. This group has led robust collective bargaining strategies, education programming, and national advocacy campaigns. Union locals have also recently bargained contracts that include “protections around pronouns, anti-harassment language, non-discrimination, health and safety” and removal of provisions that exclude transgender people from health care coverage.UFCW is committed to diverse, inclusive, and growth-oriented organizational models that affirm and promote LGBTQ+ worker members and “recognize that oppression works to undermine workers across the lines of gender, race, class, Indigeneity and sexual orientation.”UFCW OUT reach joins the movement led for more than half a century by LGBTQ+ people and advocacy groups to secure protections for LGBTQ+ people against discrimination in hiring and on the job and to ensure equal access to workplace benefits such as parental leave and equitable health care.UFCW OUT reach collaborated with the UCLA Labor Center to conduct this study to gain a deeper understanding of the current experiences, issues, challenges, and barriers that LGBTQ+ workers face across diverse industries.