Stigma Related to the Non-Medical Use and Diversion of Prescription Stimulant Drugs: Should We Care.

BACKGROUND: Non-medical use (NMU) and diversion of prescription stimulants are prevalent on college campuses. Diversion represents a primary source of acquisition for NMU among young adults. This study examined relationships between stigmatizing beliefs related to NMU and diversion of stimulant medications and engagement in these behaviors, as well as how such perceptions are associated with indicators of psychological distress among those who engage in these behaviors. METHODS: Young adults (N = 384) were recruited from a large US university to participate in this cross-sectional electronic survey-based study. Relationships between stigma variables and NMU and diversion were assessed. Among those who engage in NMU and diversion, we tested relationships between stigma variables and indicators of psychological distress, using validated instruments. RESULTS: Perceived social and personal stigmatic beliefs did not significantly predict NMU. However, perceived social and personal stigma of diversion significantly reduced diversion likelihood. For NMU, associations were found between stigma variables and indicators of psychological distress. Markedly, we found that as stigmatic perceptions of NMU increased, so did depressive, anxiolytic, and suicidal symptomatology among those who engage in NMU. CONCLUSIONS: Stigmatization does not deter NMU; however, stigmatization is positively associated with psychological harm among those who engage in NMU. Interventions should be developed to reduce stigmatization in order to improve psychological health among those who engage in NMU. Stigmatic perceptions of diversion were not predictive of psychological harm, though they are negatively associated with diversion behavior.

Salient Beliefs Associated with Unsanctioned Adult Cannabis Use in an Evolving Socio-Political Environment.

Background: The changing cannabis legal climate in the United States has been associated with increased prevalence of use, more favorable general attitudes, and cultural norms toward its use among young adults. The purpose of this study was to conceptualize salient beliefs governing illicit cannabis use within a state where medical use is legal and adult use remains illegal. Methods: Following an initial qualitative pilot, a prospective study (baseline and a 30-day follow-up) that utilized an electronic survey design was conducted. Students at a large US university (N = 514) completed a baseline assessment of cannabis use and Theory of Planned Behavior (TPB) constructs, and 169 completed the follow-up assessing actual behavior. Results: Roughly 60% reported illicit cannabis use. Attitude and subjective norms accounted for 57% of the variation in intention for cannabis use in the next 30 days, while intention and perceived behavioral control (PBC) explained 51% of the variation in prospective use. The majority of salient beliefs identified exhibited moderate to strong correlations with intention and behavior among the larger sample. Close friends and partners were identified as important referents, outcome expectations of relaxation, improved social functioning, and more enjoyment, as well as environmental factors, such as proximity to use, safe utilization location, and continued illegality of adult use exhibited strong associations to intention and behavior. Conclusions: The practical utility of the salient belief measures identified herein presents a useful foundation for interventions aimed at reducing illicit cannabis utilization among young adults.

Climate and human mortality in Virginia, 2005-2020.

Using an extensive database of every resident death in Virginia from 2005 to 2020, climate-mortality relationships are examined for 12 climatically homogeneous regions within the Commonwealth. Each region is represented by a first-order weather station from which archived temperature and humidity data are used to generate a variety of biometeorologically relevant indices. Using these indices and other variables (such as air quality and heat and cold waves), daily mortality and climate relationships are modeled for each region over a 21-day lag period utilizing generalized additive models and distributed lag non-linear models. Optimal models are identified for each region, and a consensus model was also run based on maximum temperature to facilitate inter-regional comparisons. The relative risk of mortality varies markedly as a function of climate between regions, with U-shaped, J-shaped, and inverse linear relationships evident. Cold mortality exceeds heat mortality across most of Virginia (typical relative risks are 1.10 for cold and 1.03 for heat), with cold risks strongest at lags 3 to 10. Low temperatures (or low humidity) are protective at lags 0-2 days except in the colder, western parts of state. Heat mortality occurs at short lags (0-2 days) for three-fourths of the stations, but the spatial pattern is random. Mortality displacement is evident for most regions for several days following the heat-related spike. Although the use of region-specific models is justified, the simple consensus model based on a consistent set of predictors provides similar results.

Predisposing, enabling and reinforcing factors associated with opioid addiction helping behaviour in tri-state Appalachian counties: application of the PRECEDE-PROCEED model-cross-sectional analysis.

OBJECTIVES: The overdose epidemic was designated a 'Public Health Emergency' in the USA on 26 October 2017, bringing attention to the severity of this public health problem. The Appalachian region remains substantially impacted by the effects from years of overprescription of opioids, and subsequently opioid non-medical use and addiction. This study aims to examine the utility of the PRECEDE-PROCEED model constructs (ie, predisposing, reinforcing and enabling factors) to explain opioid addiction helping behaviour (ie, helping someone who has an opioid addiction) among members of the public living in tri-state Appalachian counties. DESIGN: Cross-sectional study. SETTING: Rural county in the Appalachian region of the USA. PARTICIPANTS: A total of 213 participants from a retail mall in a rural Appalachian Kentucky county completed the survey. Most participants were between the ages of 18 and 30 years (n=68; 31.9%) and identified as men (n=139; 65.3%). PRIMARY OUTCOME MEASURE: Opioid addiction helping behaviour. RESULTS: The regression model was significant (F (6, 180)=26.191, p<0.001) and explained 44.8% of the variance in opioid addiction helping behaviour (R2=0.448). Attitude towards helping someone with opioid addiction (B=0.335; p<0.001), behavioural skills (B=0.208; p=0.003), reinforcing factors (B=0.190; p=0.015) and enabling factors (B=0.195; p=0.009) were all significantly associated with opioid addiction helping behaviour. CONCLUSIONS: PRECEDE-PROCEED model constructs have utility to explain opioid addiction helping behaviour among individuals in a region greatly impacted by the overdose epidemic. This study provides an empirically tested framework for future programmes addressing helping behaviour related to opioid non-medical use.

Lumateperone for the Treatment of Schizophrenia: Number Needed to Treat, Number Needed to Harm, and Likelihood to Be Helped or Harmed.

Objective: To describe lumateperone for the treatment of schizophrenia in adults using number needed to treat (NNT), number needed to harm (NNH), and likelihood to be helped or harmed (LHH).Methods: Data were obtained from the 3 phase 2/3 lumateperone trials, conducted between 2011 and 2016, in patients with schizophrenia diagnosed using the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision, or Fifth Edition. Efficacy was assessed using various response criteria; tolerability was principally assessed using rates of adverse events (AEs).Results: Pooled data of the 2 informative studies showed statistically significant estimates of NNT versus placebo for lumateperone 42 mg/d for the responder thresholds of ≥ 20% and ≥ 30% improvement on Positive and Negative Syndrome Scale (PANSS) total scores, with NNT for response versus placebo at 4 weeks and endpoint of 9 (95% confidence interval [CI], 5-36) and 8 (95% CI, 5-21), respectively. Pooling all studies, discontinuation because of AEs was uncommon, and the NNH versus placebo was 389 (not statistically significant from placebo [NS]). Rates of individual AEs resulted in NNH versus placebo > 10 except for somnolence/sedation (NNH of 8; 95% CI, 6-12). The occurrence of weight gain ≥ 7% from baseline yielded a NNH estimate of 122 (NS). Rates of akathisia were lower for patients receiving lumateperone compared with placebo. LHH for response versus somnolence/sedation was ~ 1 for lumateperone (similar to the risperidone active control group); otherwise, lumateperone exhibited LHH ratios that were much greater than 1 for all other AEs and that ranged from 13.6 to 48.6 for these other benefit-risk calculations.Conclusions: In 3 phase 2/3 trials, the benefit-risk assessment of lumateperone was favorable as measured by NNT, NNH, and LHH.Trial Registration: ClinicalTrials.gov identifiers: NCT01499563, NCT02282761, NCT02469155.

Adjunctive lumateperone (ITI-007) in the treatment of bipolar depression: Results from a randomized placebo-controlled clinical trial.

OBJECTIVE: This phase 3, randomized, double-blind, placebo-controlled study (NCT02600507) evaluated the efficacy and safety of lumateperone adjunctive therapy to lithium or valproate in patients with bipolar depression. METHODS: Patients (18-75 years) with bipolar I or bipolar II disorder experiencing a major depressive episode (MDE), with inadequate therapeutic response to lithium or valproate, were randomized 1:1:1 to 6 weeks adjunctive therapy with lumateperone 28 mg (n = 176), lumateperone 42 mg (n = 177), or placebo (n = 176). The primary and key secondary efficacy endpoints were change from baseline to Day 43 in Montgomery-Åsberg Depression Rating Scale (MADRS) Total score and the Clinical Global Impression Scale-Bipolar Version-Severity Scale (CGI-BP-S) depression subscore. Safety assessments included adverse events, laboratory evaluations, vital signs, extrapyramidal symptoms (EPS), and suicidality. RESULTS: Patients treated with adjunctive lumateperone 42 mg showed significantly greater improvement compared with adjunctive placebo in MADRS Total score (LS mean difference vs placebo [LSMD], -2.4; p = 0.02) and CGI-BP-S depression subscore (LSMD, -0.3; p = 0.01), while adjunctive lumateperone 28 mg showed numerical improvement in MADRS Total score (LSMD, -1.7; p = 0.10) and improvement in the CGI-BP-S depression subscore (LSMD, -0.3; p = 0.04). Adjunctive lumateperone treatment was well tolerated; treatment-emergent adverse events reported at rates >5% and twice placebo for lumateperone 42 mg were somnolence (11.3%), dizziness (10.7%), and nausea (8.5%), with minimal risk of EPS, metabolic abnormalities, or increased prolactin. CONCLUSIONS: Lumateperone 42-mg treatment adjunctive to lithium or valproate significantly improved depression symptoms and was generally well tolerated in patients with MDEs associated with either bipolar I or bipolar II disorder.

The efficacy of lumateperone on symptoms of depression in bipolar I and bipolar II disorder: Secondary and post hoc analyses.

A recent Phase 3, randomized, double-blind, placebo-controlled study established that lumateperone 42-mg monotherapy significantly improved symptoms of depression in patients with bipolar depression. This manuscript reports prespecified secondary and post hoc efficacy analyses. Patients with bipolar I or bipolar II disorder experiencing a major depressive episode were randomized 1:1 to lumateperone 42 mg or placebo, administered orally once daily for 6 weeks. Prespecified analyses evaluated change from baseline to Day 43 in individual Montgomery-Åsberg Depression Rating Scale (MADRS) item scores in the modified intent-to-treat population (mITT) and bipolar I and bipolar II disorder subgroups. Post hoc analyses investigated the MADRS anhedonia factor and categorical shifts in MADRS item scores. In the mITT, there was significant improvement from baseline to Day 43 with lumateperone 42 mg compared with placebo for all 10 MADRS items; most MADRS items significantly improved in subgroups with bipolar I (9 items) and bipolar II disorder (8 items). A significantly higher proportion of patients receiving lumateperone compared with placebo shifted from baseline MADRS item score ≥4 to ≤2 at end of treatment in Reported Sadness, Reduced Sleep, Concentration Difficulties, Lassitude, Inability to Feel, and Pessimistic Thoughts. Lumateperone significantly improved the MADRS anhedonia factor from baseline to Day 43 compared with placebo in the mITT (effect size, -0.47) and subgroups with bipolar I (-0.36) and bipolar II disorder (-0.90). Lumateperone 42 mg treatment significantly improved depression symptoms compared with placebo, with consistent efficacy across a broad range of symptoms in people with bipolar I and bipolar II disorder.

Use of the multi-theory model (MTM) in explaining initiation and sustenance of indoor tanning cessation among college students.

Skin cancer, including melanoma, is the most common cancer worldwide and a significant public health concern. A significant risk factor for melanoma is through increased exposure to ultraviolet (UV) radiation through the use of indoor tanning beds. Although rates of indoor tanning bed use have decreased in recent years, young adults, particularly White, college-age women, comprise the majority of indoor tanning bed users in the United States. The purpose of this cross-sectional study was to explore and explain the initiation and sustenance of indoor tanning cessation among college students using the multi-theory model (MTM) of health behavior change. Data were collected from 254 college students who reported current indoor tanning use using a validated 46-item survey to assess demographics and the MTM constructs. Data were analyzed using multiple linear regression to determine the ability of the MTM constructs to predict the initiation and sustenance of indoor tanning cessation. For initiation of indoor tanning cessation, participatory dialogue: advantages (B = 0.038, p = 0.001), behavioral confidence (B = 0.129, p < 0.001) and changes in the physical environment (B = 0.088, p < 0.001) were significantly associated with indoor tanning cessation following covariate adjustment. For sustenance, only emotional transformation (B = 0.140, p < 0.001) demonstrated a significant relationship with indoor tanning cessation, following adjustment. Findings from this study demonstrate the utility of the MTM in explaining indoor tanning cessation and designing intervention strategies and clinical recommendations to encourage indoor tanning cessation among college students.

Lumateperone Normalizes Pathological Levels of Acute Inflammation through Important Pathways Known to Be Involved in Mood Regulation.

Lumateperone is indicated for the treatment of schizophrenia in adults and for depressive episodes associated with bipolar I or II disorder (bipolar depression) in adults, as monotherapy and as adjunctive therapy with lithium or valproate (Calabrese et al., 2021). It is currently under evaluation for the treatment of major depressive disorder (www.ClinicalTrials.gov). Lumateperone acts by selectively modulating serotonin, dopamine, and glutamate neurotransmission in the brain. However, other mechanisms could be involved in the actions of lumateperone, and because of the connection between the immune system and psychiatric health, we hypothesized that lumateperone might improve symptoms of depression, at least in part, by normalizing pathologic inflammation. Here, we show that in male and female C57BL/6 mice subjected to an acute immune challenge, lumateperone reduced aberrantly elevated levels of key proinflammatory cytokines (e.g., IL-1ß, IL-6, and TNF-α) in both brain and serum; lumateperone also reduced proinflammatory cytokines in male mice under acute behavioral stress. Further, we demonstrate that lumateperone altered key genes/pathways involved in maintaining tissue integrity and supporting blood-brain barrier function, such as claudin-5 and intercellular adhesion molecule 1. In addition, in acutely stressed male Sprague Dawley rats, lumateperone conferred anxiolytic- and antianhedonic-like properties while enhancing activity in the mammalian target of rapamycin complex 1 pathway in the PFC. Together, our preclinical findings indicate that lumateperone, in addition to its ability to modulate multiple neurotransmitter systems, could also act by reducing the impact of acute inflammatory challenges.SIGNIFICANCE STATEMENT Lumateperone is indicated in adults to treat schizophrenia and depressive episodes associated with bipolar I or II disorder, as monotherapy and adjunctive therapy with lithium or valproate. Because aberrant immune system activity is associated with increased depressive symptoms, the relationship between lumateperone and immune function was studied. Here, lumateperone reduced the levels of proinflammatory cytokines that were increased following an immune challenge or stress in mice. Additionally, lumateperone altered genes and pathways that maintain blood-brain barrier integrity, restored an index of blood-brain barrier function, reduced anxiety-like behavior in rodents, and enhanced mammalian target of rapamycin complex 1 pathway signaling in the PFC. These results highlight the anti-inflammatory actions of lumateperone and describe how lumateperone may reduce immune pathophysiology, which is associated with depressive symptoms.

Application of the multi-theory model to explain veterinarians' intentions to use telehealth/telemedicine.

BACKGROUND: Telehealth adoption is being fueled by both technological breakthroughs and societal demands; however, veterinarians have yet to fully embrace the concept of telemedicine, limiting its use and potential benefits. The goal of this study was to evaluate how effective the multi-theory model (MTM) of health behaviour change explains the initiation and sustenance of telehealth use among veterinarians. METHODS: For this cross-sectional study, a research company was contracted to disseminate the MTM-based online survey to veterinarians currently engaged in clinical practice within the United States. RESULTS: A total of 243 veterinarians participated in this study. The most frequently reported age group among participants was 31-40 years (33.7%, n = 82). It was also noted that the majority of participants were female (70.0%, n = 170) and white (76.5%, n = 186). Hierarchical multiple regression showed that participatory dialogue (p = 0.037), species (p = 0.013) and previous monthly telehealth use (p = 0.040) were significant explanatory variables of initiation of telehealth use. Moreover, emotional transformation (p < 0.001) and previous monthly telehealth use (p = 0.035) were significant explanatory variables of sustenance of telehealth use. LIMITATIONS: The data were collected in July 2020, during a global pandemic, in which telehealth use surged across a variety of professions. As a result, the findings of the study may not be relevant in periods when there is no pandemic. CONCLUSIONS: Based on the findings of this study, researchers, educators and veterinary professionals should consider using MTM as theoretical framework to develop interventions to enhance telehealth use.

The relationship between trait emotional intelligence and problematic alcohol use among college students.

Background: Problematic alcohol use among college students is a significant public health concern. Emotional intelligence (EI), or the ability to detect one's own and others' emotions and to use this information to direct behavior, is suggested to mitigate problematic alcohol use. The purpose of this study was to examine the relationship between EI and problematic alcohol use among college students while controlling for drug use covariates. Methods: This cross-sectional study utilized an online survey comprised of previously validated measures to determine EI, problematic alcohol use, and drug use among college students from a large, public university in the south-central United States. Regression modeling and independent samples t-test were used to determine the relationship between EI and problematic alcohol use. Results: Problematic alcohol consumption was reported among 27.3% of participants (n=587). In regression modeling, EI demonstrated a significant, protective effect on problematic alcohol use (b =-0.050, P <0.001, 95% CI: -0.076 - -0.023), when adjusting for important covariates. Independent samples t-test showed that students who screened positive for harmful alcohol use reported significantly lower EI values than those who did not (Mean difference=4.53, t =2.98, P =0.003, 95% CI: 1.54-7.51). Conclusion: The findings from this study show that problematic alcohol use is prevalent among college students and EI may provide a protective effect against this deleterious behavior. Given the findings observed in this study, university officials should incorporate EI training into the university curriculum, such as in onboarding courses for freshman and transfer students, to target prevention of potentially harmful alcohol consumption and associated negative health impacts.

Osteoporosis knowledge and health beliefs among middle-aged men and women in the Southern United States.

CONTEXT: The most common skeletal disease, osteoporosis, causes bone fragility due to decreased bone mass and bone microarchitecture destruction. The health belief model is often applied to asymptomatic, prevention-related diseases such as osteoporosis. Steps to mitigate the insidious nature of osteoporosis, including education, motivation, and monitoring of bone mineral density, must begin at an earlier age. OBJECTIVES: This study evaluates the knowledge and health beliefs surrounding osteoporosis in a population of males and females 35-50 years old to determine sex-based differences in osteoporosis knowledge and beliefs and to assess the correlation between perceptions and health motivation. METHODS: Participants (81 males, 92 females) completed two questionnaires: the Osteoporosis Knowledge Test and the Osteoporosis Health Belief Scale. Descriptive statistics were performed along with Pearson product-moment correlation analysis to determine the relationships between the variables. Sex-based differences were calculated utilizing independent t-tests. RESULTS: We discovered a statistically significant negative correlation between the barriers to exercise and health motivation (-0.434, p < 0.001) and a statistically significant positive correlation between the benefits of exercise and health motivation (0.385, p < 0.001). However, there was not a statistically significant correlation between health motivation with the following: the benefits of calcium, susceptibility, and the seriousness of osteoporosis. Between males and females, there was a statistically significant difference in exercise and calcium knowledge, susceptibility, and the benefits of both exercise and calcium (p < 0.05). CONCLUSIONS: Males and females 35-50 years old perceive themselves to have a low susceptibility to osteoporosis. They do not consider osteoporosis a serious disease and have little motivation to mitigate its inception or progression. Their perceptions show that barriers to exercise impact health motivation more than the perceived benefits of exercise.

The Association between Weather and Emergency Department Visitation for Diabetes in Roanoke, Virginia.

Diabetes mellitus imposes a significant and increasing health burden on the US population. Our objective is to determine if weather is related to daily variations in emergency department (ED) visits for diabetes mellitus in Roanoke, Virginia. A time series of daily ED visits for diabetes mellitus at the Carilion Clinic in southwestern Virginia is associated with daily minimum temperature from 2010-2017. Associations between ED visits (through a 14-day lag period) and temperature are examined using generalized additive models and distributed lag nonlinear models. Heat and cold waves are identified at low and high thresholds, and ED visitation during these events is compared to prior control periods using a time-stratified case crossover approach. ED visits for diabetes exhibit a U-shaped relationship with temperature, with a higher relative risk (RR) during cold events (RR = 1.05) vs. warm events (RR = 1.02). When minimum temperatures are below freezing, ED visitation peaks starting 2 days afterward, with RRs approaching 1.04. The RR on warm days (minimum temperature > 10 °C) approaches 1.02 but peaks on the day of or the day following the elevated temperatures. Cold waves increase the odds of ED visits by up to 11% (p = 0.01), whereas heat waves exhibit no significant effect (p = 0.07). The increasing health burden linked to diabetes requires new research on environmental factors that might exacerbate related illness. When examined in the context of climate change impacts on local weather variations, these kinds of linkages between environment and disease can aid in facility staffing and public health messaging during extreme weather events.

Single doses of a highly selective inhibitor of phosphodiesterase 1 (lenrispodun) in healthy volunteers: a randomized pharmaco-fMRI clinical trial.

Lenrispodun is a potent and highly selective inhibitor of phosphodiesterase (PDE) type 1, which is thought to prolong intracellular second messenger signaling within cortical and subcortical dopaminergic brain regions. This is the first study of a PDE1 inhibitor in healthy volunteers using behavioral and neuroimaging approaches to examine its effects on neural targets and to provide a safety and tolerability assessment. The primary objectives were to determine whether lenrispodun induces changes in BOLD fMRI signals in the inferior frontal gyrus (IFG) during the stop signal task, and the dorsal anterior insula (dAI) during the extinction phase of a fear conditioning/extinction task. Using a double-blind, placebo-controlled, within-subjects design, 26 healthy individuals (22 completed all fMRI sessions) received in random order a single oral dose of placebo, lenrispodun 1.0 milligram (mg) or lenrispodun 10.0 mg and completed several tasks in the scanner including the stop signal (n = 24) and fear conditioning/extinction tasks (n = 22). Prespecified region-of-interest analyses for the IFG and dAI were computed using linear mixed models. Lenrispodun induced increases in IFG activity during the stop signal task at 1.0 mg (Cohen's d = 0.63) but not 10.0 mg (Cohen's d = 0.07) vs. placebo. Lenrispodun did not induce changes in dAI activity during fear extinction at either dose. Exploratory outcomes revealed changes in cardiac interoception. Lenrispodun administration was well-tolerated. These results provide evidence that 1.0 mg lenrispodun selectively improved neural inhibitory control without altering fear extinction processing. Future investigations should determine whether lenrispodun improves inhibitory control in target populations such as individuals with attention deficit hyperactivity disorder. Trial registration: ClinicalTrials.gov identifier: NCT03489772.

The impact of cold weather on respiratory morbidity at Emory Healthcare in Atlanta.

BACKGROUND: Research on temperature and respiratory hospitalizations is lacking in the southeastern U.S. where cold weather is relatively rare. This retrospective study examined the association between cold waves and pneumonia and influenza (P&I) emergency department (ED) visits and hospitalizations in three metro-Atlanta hospitals. METHODS: We used a case-crossover design, restricting data to the cooler seasons of 2009-2019, to determine whether cold waves influenced ED visits and hospitalizations. This analysis considered effects by race/ethnicity, age, sex, and severity of comorbidities. We used generalized additive models and distributed lag non-linear models to examine these relationships over a 21-day lag period. RESULTS: The odds of a P&I ED visit approximately one week after a cold wave were increased by as much as 11%, and odds of an ED visit resulting in hospitalization increased by 8%. For ED visits on days with minimum temperatures >20 °C, there was an increase of 10-15% in relative risk (RR) for short lags (0-2 days), and a slight decrease in RR (0-5%) one week later. For minimum temperatures <0 °C, RR decreased at short lags (5-10%) before increasing (1-5%) one week later. Hospital admissions exhibited a similar, but muted, pattern. CONCLUSION: Unusually cold weather influenced P&I ED visits and admissions in this population.

Analyzing Twitter Chatter About Tobacco Use Within Intoxication-related Contexts of Alcohol Use: "Can Someone Tell Me Why Nicotine is So Fire When You're Drunk?"

INTRODUCTION: Alcohol and tobacco are commonly used together. Social influences within online social networking platforms contribute to youth and young adult substance use behaviors. This study used a sample of alcohol- and tobacco-related tweets to evaluate: (1) sentiment toward co-use of alcohol and tobacco, (2) increased susceptibility to tobacco use when consuming alcohol, and (3) the role of alcohol in contributing to a failed attempt to quit tobacco use. METHODS: Data were collected from the Twitter API from January 1, 2019 through December 31, 2019 using tobacco-related keywords (e.g., vape, ecig, smoking, juul*) and alcohol-related filters (e.g., drunk, blackout*). A total of 78,235 tweets were collected, from which a random subsample (n = 1,564) was drawn for coding. Cohen's Kappa values ranged from 0.66 to 0.99. RESULTS: Most tweets were pro co-use of alcohol and tobacco (75%). One of every ten tweets reported increased susceptibility to tobacco use when intoxicated. Non-regular tobacco users reported cravings for and tobacco use when consuming alcohol despite disliking tobacco use factors such as the taste, smell, and/or negative health effects. Regular tobacco users reported using markedly higher quantities of tobacco when intoxicated. Individuals discussed the role of alcohol undermining tobacco cessation attempts less often (2.0%), though some who had quit smoking for prolonged periods of time reported reinitiating tobacco use during acute intoxication episodes. CONCLUSIONS: Tobacco cessation interventions may benefit from including alcohol-focused components designed to educate participants about the association between increased susceptibility to tobacco use when consuming alcohol and the role of alcohol in undermining tobacco cessation attempts. IMPLICATIONS: Sentiment toward co-use of alcohol and tobacco on Twitter is largely positive. Individuals reported regret about using tobacco, or using more than intended, when intoxicated. Those who had quit smoking or vaping for prolonged periods of time reported reinitiating tobacco use when consuming alcohol. While social media-based tobacco cessation interventions like the Truth Initiative's "Ditch the Juul" campaign demonstrate potential to change tobacco use behaviors, these campaigns may benefit from including alcohol-focused components designed to educate participants about the association between increased susceptibility to tobacco use when consuming alcohol and the role of alcohol in undermining tobacco cessation attempts.

Efficacy and Safety of Lumateperone for Major Depressive Episodes Associated With Bipolar I or Bipolar II Disorder: A Phase 3 Randomized Placebo-Controlled Trial.

OBJECTIVE: In a phase 3 randomized double-blind placebo-controlled study, the authors investigated the efficacy and safety of 42 mg/day of lumateperone in patients with bipolar I or bipolar II disorder experiencing a major depressive episode. METHODS: Patients 18-75 years old with a clinical diagnosis of bipolar I or bipolar II disorder and experiencing a major depressive episode were eligible for the study. Patients were randomized in a 1:1 ratio to receive 42 mg/day of lumateperone (N=188) or placebo (N=189), administered orally once daily in the evening for 6 weeks. The primary and key secondary efficacy endpoints were change from baseline to day 43 in score on the Montgomery-Åsberg Depression Rating Scale (MADRS) and total score on the Clinical Global Impressions Scale-Bipolar Version severity scale (CGI-BP-S), respectively. Safety assessments included treatment-emergent adverse events, laboratory parameters, vital signs, extrapyramidal symptoms, and suicidality. RESULTS: At day 43, lumateperone treatment was associated with significantly greater improvement from baseline in MADRS score compared with placebo (least squares mean difference compared with placebo, -4.6 points; effect size=-0.56) and CGI-BP-S total score (least squares mean difference compared with placebo, -0.9; effect size=-0.46). Significant MADRS superiority for lumateperone over placebo was observed both in patients with bipolar I and bipolar II disorders. Somnolence and nausea were the only treatment-emergent adverse events that occurred with lumateperone at a clinically meaningful greater rate than placebo. The incidence of extrapyramidal symptom-related treatment-emergent adverse events was low and similar to that for placebo. Minimal changes were observed in weight, vital signs, or metabolic or endocrine assessments. CONCLUSIONS: Lumateperone at 42 mg/day significantly improved depression symptoms and was generally well tolerated in patients with major depressive episodes associated with both bipolar I and bipolar II disorders.

Vascular Ageing Features Caused by Selective DNA Damage in Smooth Muscle Cell.

Persistently unrepaired DNA damage has been identified as a causative factor for vascular ageing. We have previously shown that a defect in the function or expression of the DNA repair endonuclease ERCC1 (excision repair cross complement 1) in mice leads to accelerated, nonatherosclerotic ageing of the vascular system from as early as 8 weeks after birth. Removal of ERCC1 from endothelial alone partly explains this ageing, as shown in endothelial-specific Ercc1 knockout mice. In this study, we determined vascular ageing due to DNA damage in vascular smooth muscle cells, as achieved by smooth muscle-selective genetic removal of ERCC1 DNA repair in mice (SMC-KO: SM22αCre+ Ercc1fl/-). Vascular ageing features in SMC-KO and their wild-type littermates (WT: SM22αCre+ Ercc1fl/+) were examined at the age of 14 weeks and 25 weeks. Both SMC-KO and WT mice were normotensive. Compared to WT, SMC-KO showed a reduced heart rate, fractional shortening, and cardiac output. SMC-KO showed progressive features of nonatherosclerotic vascular ageing as they aged from 14 to 25 weeks. Decreased subcutaneous microvascular dilatation and increased carotid artery stiffness were observed. Vasodilator responses measured in aortic rings in organ baths showed decreased endothelium-dependent and endothelium-independent responses, mostly due to decreased NO-cGMP signaling. NADPH oxidase 2 and phosphodiesterase 1 inhibition improved dilations. SMC-KO mice showed elevated levels of various cytokines that indicate a balance shift in pro- and anti-inflammatory pathways. In conclusion, SMC-KO mice showed a progressive vascular ageing phenotype in resistant and conduit arteries that is associated with cardiac remodeling and contractile dysfunction. The changes induced by DNA damage might be limited to VSMC but eventually affect EC-mediated responses. The fact that NADPH oxidase 2 as wells as phosphodiesterase 1 inhibition restores vasodilation suggests that both decreased NO bioavailability and cGMP degradation play a role in local vascular smooth muscle cell ageing induced by DNA damage.

#Alcohol: Portrayals of Alcohol in Top Videos on TikTok.

OBJECTIVE: The purpose of this study was to characterize the content and themes present in user-generated TikTok videos portraying alcohol. METHOD: We captured the 100 most popular videos including the #alcohol hashtag on the popular social networking site TikTok. We used an iterative process to codebook development, resulting in codes for user sentiment toward alcohol, type of alcohol depicted, brand references, degree of alcohol use, and positive/negative associations with alcohol use. Videos were independently double coded, evaluated for inter-rater agreement, and adjudicated if differences were present. RESULTS: The videos in our sample were collectively viewed 291,999,100 times. The vast majority (98%) of videos expressed pro-alcohol sentiment. Nearly half of videos (41%) were guide videos demonstrating drink recipes. The majority of videos (72%) included liquor. Consuming multiple drinks quickly was depicted in more than half of videos (61%), whereas intoxication (13%) was exhibited less frequently. Positive associations with alcohol were prevalent; 69% of videos conveyed positive experiences with alcohol, 55% of videos contained humor, and 45% included associations of alcohol with camaraderie. Negative associations with alcohol were rarely portrayed (4%). CONCLUSIONS: Top alcohol-related videos on TikTok are heavily viewed. Their contents demonstrate a propensity to promote rapid consumption of multiple drinks and to juxtapose alcohol use with positive associations such as humor and camaraderie, while rarely depicting negative outcomes associated with hazardous alcohol use.