The e-cigarette assessment for youth-Revised (EAsY-R): Preliminary results of a pilot study of measure refinement via cognitive interviewing.

The prevalence of youth vaping has, in a relatively short time, become an "epidemic." In the wake of such labeling by the Surgeon General, a number of important examinations of vaping have been conducted. These have largely focused on high school and college-age youth as this demographic shows the greatest prevalence of use. Nonetheless, no measure has been made available which might allow for the comprehensive assessment of quantity and frequency of vaping among this age group, thus aiding in standardization across settings. The current study utilized cognitive interviews with high school and college-age youth who use vaping devices to inform the preliminary development of such an assessment. The sample consists of eight students between the ages of 15 and 24 (Mage = 18.75, SD = 2.73, 62.5% female, 75.0% Hispanic/Latino/a/x, 100.0% White). Interviewing and measure refinement were conducted in a two-phase iterative fashion. Suggestions made during cognitive interviews resulted in the refinement of assessed content type, updated categories and pictures of vaping devices, as well as updated and age-relevant terminology. Further, instructions were streamlined, and assessment items and multiple-choice options were refined to maximize clarity and to minimize participant confusion. The result of this study, the E-Cigarette Assessment for Youth Revised, is a unique tool for standardizing examinations of the quantity and frequency of vaping behaviors among high school students and college-age youth.

Smoothness as a quality of care: An STS approach to transnational healthcare mediation.

Medical travel and transnational healthcare involve various difficulties such as the distance and disconnect between patients and healthcare providers, language barriers or logistical challenges of moving ill bodies across space. Medical travel facilitation steps in with some sort of brokerage service that contributes to overcoming or managing these difficulties and, as this paper suggests, acts to create a quality of 'smoothness'. By unpacking three salient facilitation practices, namely connecting, communicating, and coordinating, this paper conceptualises the empirically derived category of 'smoothness'. This as a disposition, outcome, and spatio-temporal manoeuvre of medical travel facilitation. Based on the way in which such practices of mediation act to create smoothness, namely in an attentive, persistent, and collective tinkering manner, this paper suggests that some practices of medical travel facilitation are productively thought not just about setting up the possibility of care transnationally, but that they are key forms of care in itself. Based on these findings, smoothness is considered to be a central but also contested quality of medical travel facilitation and brokerage in a broader sense, but as proposed here, also for care. This conclusion potentially has implications not just for the study of transnational healthcare and mediation activities, but also that of care and transnational mobilities more generally.

The Role of Socialization Contexts on Adolescent Substance Use across Racial and Ethnic Groups.

Purpose of Review: This review summarizes theories and empirical work regarding socialization contexts contributing to substance use across marginalized adolescents. Future directions and recommendations to minimize the perpetuation of racial stereotypes are provided. Recent Findings: Neighborhoods high in social cohesion may offset substance use risk. Promoting school connectedness via increased support from teachers and peers could reduce school-based discrimination and enhance feelings of belongingness. The influence of peers on substance use engagement largely differs across racial groups and level of acculturation. Family cultural values emphasizing respect, obedience, and collectivism offer protection from substance use. Summary: Despite lower prevalence rates of adolescent substance use within racial/ethnic groups, rates of negative consequences due to substances are far greater compared to White adolescents. Transcultural factors (e.g., strong family ties), as well as culture-specific factors, should be leveraged to delay the onset of substance use and prevent negative sequelae resulting from substance use initiation.

Risk factors for early use of e-cigarettes and alcohol: Dimensions and profiles of temperament.

Adolescent e-cigarette use has been labeled an epidemic and alcohol use during this developmental period is associated with deleterious outcomes. Though specific temperamental dimensions have been shown to predict substance use, profiles of temperament have rarely been examined as predictors. This study examines dimensions and profiles of adolescent temperament as predictors of early use of e-cigarettes and alcohol. The sample was comprised of adolescent (62.07% female, 87.59% White, 82.76% Hispanic/Latinx)/caregiver dyads (N = 146) who completed the first two timepoints (M age at second timepoint = 16.16, SD = 0.68) of a longitudinal adolescent substance use study. Models showed parent-reported effortful control predicted protection against adolescent use of e-cigarettes, whereas adolescent report of effortful control predicted protection against alcohol use. Though dissimilar in temperamental pattern, three profiles emerged from both parent- and adolescent-report-based latent profile analysis models. Adolescents characterized by parents as displaying a Resilient profile had greater odds of e-cigarette use than those characterized by a Reserved profile, whereas adolescents who self-characterized as Mixed-type had markedly greater odds of alcohol use than those who self-characterized as Resilient. Utilization of temperamental profiles may aid in identification of particularly vulnerable subgroups of adolescents who may benefit from relevant preventative programing.

Sodium-Glucose Co-Transporter-2 Inhibitors and Cardiac Outcomes Among Patients Treated With Anthracyclines.

BACKGROUND: Sodium-glucose co-transporter-2 (SGLT2) inhibitors improve outcomes among patients with established heart failure. Despite supportive basic science studies, there are no data on the value of SGLT2 inhibitors among patients treated with anthracyclines. OBJECTIVES: This study sought to test the cardiac efficacy and overall safety of SGLT2 inhibitors in patients treated with anthracyclines. METHODS: This study identified 3,033 patients with diabetes mellitus (DM) and cancer who were treated with anthracyclines. Cases were patients with cancer and DM who were on SGLT2 inhibitor therapy during anthracycline treatment (n = 32). Control participants (n = 96) were patients with cancer and DM who were also treated with anthracyclines, but were not on an SGLT2 inhibitor. The primary cardiac outcome was a composite of cardiac events (heart failure incidence, heart failure admissions, new cardiomyopathy [>10% decline in ejection fraction to <53%], and clinically significant arrhythmias). The primary safety outcome was overall mortality. RESULTS: Age, sex, ethnicity, cancer type, cancer stage, and other cardiac risk factors were similar between groups. There were 20 cardiac events over a median follow-up period of 1.5 years. The cardiac event incidence was lower among case patients in comparison to control participants (3% vs 20%; P = 0.025). Case patients also experienced lower overall mortality when compared with control participants (9% vs 43%; P < 0.001) and a lower composite of sepsis and neutropenic fever (16% vs 40%; P = 0.013). CONCLUSIONS: SGLT2 inhibitors were associated with lower rate of cardiac events among patients with cancer and DM who were treated with anthracyclines. Additionally, SGLT2 inhibitors appeared to be safe. These data support the conducting of a randomized clinical trial testing SGLT2 inhibitors in patients at high cardiac risk treated with anthracyclines.

Silver nanoparticles adversely affect the swimming behavior of European Whitefish (Coregonus lavaretus) larvae within the low µg/L range.

The aim of this study was to determine the effects of silver nanoparticles (AgNPs; speciation: NM-300 K) in the lab on the behavior of larvae in European Whitefish (Coregonus lavaretus), a relevant model species for temperate aquatic environments during alternating light and darkness phases. The behavioral parameters measured included activity, turning rate, and distance moved. C. lavaretus were exposed to AgNP at nominal concentrations of 0, 5, 15, 45, 135, or 405 µg/L (n = 33, each) and behavior was recorded using a custom-built tracking system equipped with light sources that reliably simulate light and darkness. The observed behavior was analyzed using generalized linear mixed models, which enabled reliable detection of AgNP-related movement patterns at 10-fold higher sensitivity compared to recently reported standard toxicological studies. Exposure to 45 µg/L AgNPs significantly resulted in hyperactive response patterns for both activity and turning rates after an illumination change from light to darkness suggesting that exposure to this compound triggered escape mechanisms and disorientation-like behaviors in C. lavaretus fish larvae. Even at 5 µg/L AgNPs some behavioral effects were detected, but further tests are required to assess their ecological relevance. Further, the behavior of fish larvae exposed to 135 µg/L AgNPs was comparable to the control for all test parameters, suggesting a triphasic dose response pattern. Data demonstrated the potential of combining generalized linear mixed models with behavioral investigations to detect adverse effects on aquatic species that might be overlooked using standard toxicological tests.

The efficacy and safety of cardio-protective therapy in patients with 5-FU (Fluorouracil)-associated coronary vasospasm.

BACKGROUND: Coronary vasospasm is a known side effect of 5-FU (fluorouracil) therapy. Beyond switching to non-5FU-based chemotherapy, there are no established treatments for 5-FU associated coronary vasospam. Our objective was to assess the safety and efficacy of re-challenge with 5-FU after pre-treatment with calcium channel blockers (CCBs) and long-acting nitrates among patients 5-FU associated coronary vasospasm. METHODS: We conducted a retrospective study of patients with 5-FU coronary vasospasm at a single academic center. By protocol, those referred to cardio-oncology received pre-treatment with either combination [nitrates and CCBs] or single-agent therapy [nitrates or CCBs]) prior to re-challenge with 5-FU. Our primary outcome was overall survival. Other important outcomes included progression-free survival and safety. RESULTS: Among 6,606 patients who received 5-FU from January 2001 to Dec 2020, 115 (1.74%) developed coronary vasospasm. Of these 115 patients, 81 patients continued 5-FU therapy, while 34 stopped. Of the 81 who continued, 78 were referred to cardio-oncology and prescribed CCBs and/or nitrates prior to subsequent 5-FU, while the remaining 3 continued 5-FU without cardiac pre-treatment. Of the 78, 56.4% (44/78) received both nitrates and CCBs, 19.2% (15/78) received CCBs alone, and 24.4% (19/78) received nitrates alone. When compared to patients who stopped 5-FU, those who continued 5-FU after pre-treatment (single or combination therapy) had a decreased risk of death (HR 0.42, P = 0.005 [95% CI 0.23-0.77]) and a trend towards decreased cancer progression (HR 0.60, P = 0.08 [95% CI 0.34-1.06]). No patient in the pre-treatment group had a myocardial infarct after re-challenge; however, chest pain (without myocardial infarction) recurred in 19.2% (15/78) among those who received cardiac pre-treatment vs. 66.7% (2/3) among those who did not (P = 0.048). There was no difference in efficacy or the recurrence of vasospasm among patients who received pre-treatment with a single agent (nitrates or CCBs) or combination therapy (14.7% (5/34) vs. 25.0% (11/44), P = 0.26). CONCLUSION: Re-challenge after pre-treatment with CCBs and nitrates guided by a cardio-oncology service was safe and allowed continued 5-FU therapy.

The Impact of COVID-19 Experiences on Adolescent Internalizing Problems and Substance Use Among a Predominantly Latinx Sample.

Given the salience of socialization factors on adolescence and their role in vulnerability to disasters and trauma, this study examined whether COVID-19-associated fears and impacted quality of life mediated associations between pandemic-focused family conversations and media exposure and subsequent youth mental health. A primarily Latinx sample of adolescents (N = 167; Mage = 16.2 years, 44.9% female) participated in a longitudinal (summer 2020-winter 2020) COVID-19 study. COVID-19 media exposure predicted engagement in relevant safety behaviors, which negatively impacted quality of life, which in turn predicted increased internalizing problems. COVID-19 family conversations predicted social distancing fears, which negatively impacted quality of life, which then in turn also predicted increased internalizing problems. Targeting key socialization factors may minimize negative consequences following major community trauma among adolescents.

Tolerance for specific negative affective states and coping-oriented cannabis use motives among college student cannabis users.

ObjectiveThe current study examined the unique predictive ability of tolerance of specific negative affective states in relation to frequency of past-month cannabis use and coping-oriented cannabis use motives. Participants: 416 undergraduates who reported past 30 day cannabis use (65.1% female; Mage = 19.46, SD = 2.56). Methods: Participants completed self-report questionnaires for course credit. Results: After accounting for the effects of sex, negative affectivity, and tolerance of other specific negative affective states, lower levels of tolerance for sadness, but not any other negative affective states, significantly predicted more frequent cannabis use in the past 30 days (1.1% unique variance) and coping motives (1.1% unique variance). Conclusions: These findings suggest that cannabis users who have difficulty withstanding sad mood states use cannabis more frequently and are motivated to use cannabis to cope with this specific mood state and not necessarily negative affective states more broadly.

Pre-Existing Autoimmune Disease Increases the Risk of Cardiovascular and Noncardiovascular Events After Immunotherapy.

Background: The use of immune checkpoint inhibitors (ICI) is associated with cardiovascular (CV) events, and patients with pre-existing autoimmune disease are at increased CV risk. Objectives: The aim of this study was to characterize the risk for CV events in patients with pre-existing autoimmune disease post-ICI. Methods: This was a retrospective study of 6,683 patients treated with ICIs within an academic network. Autoimmune disease prior to ICI was confirmed by chart review. Baseline characteristics and risk for CV and non-CV immune-related adverse events were compared with a matched control group (1:1 ratio) of ICI patients without autoimmune disease. Matching was based on age, sex, history of coronary artery disease, history of heart failure, and diabetes mellitus. CV events were a composite of myocardial infarction, percutaneous coronary intervention, coronary artery bypass graft, stroke, transient ischemic attack, deep venous thrombosis, pulmonary embolism, or myocarditis. Univariable and multivariable Cox proportional hazards models were used to determine the association between autoimmune disease and CV events. Results: Among 502 patients treated with ICIs, 251 patients with and 251 patients without autoimmune disease were studied. During a median follow-up period of 205 days, there were 45 CV events among patients with autoimmune disease and 22 CV events among control subjects (adjusted HR: 1.77; 95% CI: 1.04-3.03; P = 0.0364). Of the non-CV immune-related adverse events, there were increased rates of psoriasis (11.2% vs 0.4%; P < 0.001) and colitis (24.3% vs 16.7%; P = 0.045) in patients with autoimmune disease. Conclusions: Patients with autoimmune disease have an increased risk for CV and non-CV events post-ICI.

Immune checkpoint inhibitors for cancer and venous thromboembolic events.

BACKGROUND: Immune checkpoint inhibitors (ICIs) are widely used cancer treatments. There are limited data on the risk for developing venous thromboembolism (VTE) among patients on an ICI. METHODS: This was a retrospective study of 2854 patients who received ICIs at a single academic centre. VTE events, defined as a composite of deep vein thrombosis or pulmonary embolism, were identified by individual chart review and blindly adjudicated using standard imaging criteria. A self-controlled risk-interval design was applied with an 'at-risk period' defined as the two-year period after and the 'control period', defined as the two-year before treatment. The hazard ratio (HR) was calculated using a fixed-effect proportional hazards model. RESULTS: Of the 2854 patients, 1640 (57.5%) were men; the mean age was 64 ± 13 years. The risk for VTE was 7.4% at 6 months and 13.8% at 1 year after starting an ICI. The rate of VTE was > 4-fold higher after starting an ICI (HR 4.98, 95% CI 3.65-8.59, p < 0.001). There was a 5.7-fold higher risk for deep vein thrombosis (HR 5.70, 95% CI 3.79-8.59, p < 0.001) and a 4.75-fold higher risk for pulmonary embolism (HR 4.75, 95% CI 3.20-7.10, p < 0.001). Comparing patients with and without a VTE event, a history of melanoma and older age predicted lower risk of VTE, while a higher Khorana risk score, history of hypertension and history of VTE predicted higher risk. CONCLUSIONS: The rate of VTE among patients on an ICI is high and increases after starting an ICI.

Association between incidental statin use and skeletal myopathies in patients treated with immune checkpoint inhibitors.

OBJECTIVES: Skeletal myopathies are highly morbid, and in rare cases even fatal, immune-related adverse events (irAE) associated with immune checkpoint inhibitors (ICI). Skeletal myopathies are also a recognized statin-associated side effect. It is unknown whether concurrent use of statins and ICIs increases the risk of skeletal myopathies. METHODS: This was a retrospective cohort study of all patients who were treated with an ICI at a single academic institution (Massachusetts General Hospital, Boston, MA, USA). The primary outcome of interest was the development of a skeletal myopathy. The secondary outcome of interest was an elevated creatine kinase level (above the upper limit of normal). RESULTS: Among 2757 patients, 861 (31.2%) were treated with a statin at the time of ICI start. Statin users were older, more likely to be male and had a higher prevalence of cardiovascular and non-cardiovascular co-morbidities. During a median follow-up of 194 days (inter quartile range 65-410), a skeletal myopathy occurred in 33 patients (1.2%) and was more common among statin users (2.7 vs. 0.9%, P < 0.001). Creatine kinase (CK) elevation was present in 16.3% (114/699) and was higher among statin users (20.0 vs. 14.3%, P = 0.067). In a multivariable Cox model, statin therapy was associated with a >2-fold higher risk for skeletal myopathy (HR, 2.19; 95% confidence interval, 1.07-4.50; P = 0.033). CONCLUSION: In this large cohort of ICI-treated patients, a higher risk was observed for skeletal myopathies and elevation in CK levels in patients undergoing concurrent statin therapy. Prospective observational studies are warranted to further elucidate the potential association between statin use and ICI-associated myopathies.

Pericardial disease in patients treated with immune checkpoint inhibitors.

BACKGROUND: There are limited data on the occurrence, associations and outcomes of pericardial effusions and pericarditis on or after treatment with immune checkpoint inhibitors (ICIs). METHODS: This was a retrospective study at a single academic center that compared 2842 consecutive patients who received ICIs with 2699 age- and cancer-type matched patients with metastatic disease who did not receive ICI. A pericardial event was defined as a composite outcome of pericarditis and new or worsening moderate or large pericardial effusion. The endpoints were obtained through chart review and were blindly adjudicated. To identify risk factors associated with a pericardial event, we compared patients who developed an event on an ICI with patients treated with an ICI who did not develop a pericardial event. Cox proportional-hazard model and logistical regression analysis were performed to study the association between ICI use and pericardial disease as well as pericardial disease and mortality. An additional 6-week landmark analysis was performed to account for lead-time bias. RESULTS: There were 42 pericardial events in the patients treated with ICI (n=2842) over 193 days (IQR: 64-411), yielding an incidence rate of 1.57 events per 100 person-years. There was a more than fourfold increase in risk of pericarditis or a pericardial effusion among patients on an ICI compared with controls not treated with ICI after adjusting for potential confounders (HR 4.37, 95% CI 2.09 to 9.14, p<0.001). Patients who developed pericardial disease while on an ICI had a trend for increased all-cause mortality compared with patients who did not develop a pericardial event (HR 1.53, 95% CI 0.99 to 2.36, p=0.05). When comparing those who developed pericardial disease after ICI treatment with those who did not, a higher dose of corticosteroid pre-ICI (>0.7 mg/kg prednisone) was associated with increased risk of pericardial disease (HR 2.56, 95% CI 1.00 to 6.57, p=0.049). CONCLUSIONS: ICI use was associated with an increased risk of development of pericardial disease among patients with cancer and a pericardial event on an ICI was associated with a trend towards increase in mortality.

The Incidence, Risk Factors, and Outcomes With 5-Fluorouracil-Associated Coronary Vasospasm.

BACKGROUND: Coronary vasospasm is a recognized side effect of 5-FU (fluorouracil). There are limited and conflicting data on the incidence, risk factors and prognostic effect of 5-FU associated vasospasm. OBJECTIVES: To assess the incidence, risk factors and prognostic implications of 5-FU coronary vasospasm among patients receiving 5-FU regimens at a single tertiary care center. METHODS: We conducted a retrospective analysis of all patients who received 5-FU at a single academic center from January 2009 to July 2019. Vasospasm was defined as the occurrence of a typical chest pain syndrome in the presence of 5-FU. The presence of associated electrocardiogram (ECG) changes and/or elevated biomarkers was used to further confirm the diagnosis. Patients with vasospasm were compared to patients treated with 5-FU without vasospasm in a 1:2 ratio. Data regarding demographics, medical history, and follow-up were collected by manual chart review. RESULTS: From approximately 4019 individual patients who received 5-FU from 2009 to 2019 at a single center, 87 (2.16%) developed vasospasm. Patients who developed vasospasm were younger (58±13 vs. 64±13 years, P = 0.001), and were less likely to have any cardiovascular risk factors (70.1% vs. 84.5%, P = 0.007). Patients with vasospasm and patients without vasospasm were otherwise similar in terms of types of cancer, stage of cancer, sex, and race. There was no significant difference in progression-free survival, overall mortality or cancer specific mortality between patients who developed vasospasm versus those who did not. CONCLUSION: In a large, single-center report of 5-FU associated vasospasm, patients who developed vasospasm were younger, had lower rates of traditional cardiovascular risk factors and had no significant difference in progression-free or overall survival compared to those who did not develop vasospasm.

Myocardial T1 and T2 Mapping by Magnetic Resonance in Patients With Immune Checkpoint Inhibitor-Associated Myocarditis.

BACKGROUND: Myocarditis is a potentially fatal complication of immune checkpoint inhibitor (ICI) therapy. Data on the utility of cardiovascular magnetic resonance (CMR) T1 and T2 mapping in ICI myocarditis are limited. OBJECTIVES: This study sought to assess the value of CMR T1 and T2 mapping in patients with ICI myocarditis. METHODS: In this retrospective study from an international registry of patients with ICI myocarditis, clinical and CMR findings (including T1 and T2 maps) were collected. Abnormal T1 and T2 were defined as 2 SD above site (vendor/field strength specific) reference values and a z-score was calculated for each patient. Major adverse cardiovascular events (MACE) were a composite of cardiovascular death, cardiogenic shock, cardiac arrest, and complete heart block. RESULTS: Of 136 patients with ICI myocarditis with a CMR, 86 (63%) had T1 maps and 79 (58%) also had T2 maps. Among the 86 patients (66.3 ± 13.1 years of age), 36 (41.9%) had a left ventricular ejection fraction <55%. Across all patients, mean z-scores for T1 and T2 values were 2.9 ± 1.9 (p < 0.001) and 2.2 ± 2.1 (p < 0.001), respectively. On Siemens 1.5-T scanner (n = 67), native T1 (1,079.0 ± 55.5 ms vs. 1,000.3 ± 22.1 ms; p < 0.001) and T2 (56.2 ± 4.9 ms vs. 49.8 ± 2.2 ms; p < 0.001) values were elevated compared with reference values. Abnormal T1 and T2 values were seen in 78% and 43% of the patients, respectively. Applying the modified Lake Louise Criteria, 95% met the nonischemic myocardial injury criteria and 53% met the myocardial edema criteria. Native T1 values had excellent discriminatory value for subsequent MACE, with an area under the curve of 0.91 (95% confidence interval: 0.84 to 0.98). Native T1 values (for every 1-unit increase in z-score, hazard ratio: 1.44; 95% confidence interval: 1.12 to 1.84; p = 0.004) but not T2 values were independently associated with subsequent MACE. CONCLUSIONS: The use of T1 mapping and application of the modified Lake Louise Criteria provides important diagnostic value, and T1 mapping provides prognostic value in patients with ICI myocarditis.

Electrocardiographic features of immune checkpoint inhibitor associated myocarditis.

BACKGROUND: Myocarditis is a highly morbid complication of immune checkpoint inhibitor (ICI) use that remains inadequately characterized. The QRS duration and the QTc interval are standardized electrocardiographic measures that are prolonged in other cardiac conditions; however, there are no data on their utility in ICI myocarditis. METHODS: From an international registry, ECG parameters were compared between 140 myocarditis cases and 179 controls across multiple time points (pre-ICI, on ICI prior to myocarditis, and at the time of myocarditis). The association between ECG values and major adverse cardiac events (MACE) was also tested. RESULTS: Both the QRS duration and QTc interval were similar between cases and controls prior to myocarditis. When compared with controls on an ICI (93±19 ms) or to baseline prior to myocarditis (97±19 ms), the QRS duration prolonged with myocarditis (110±22 ms, p<0.001 and p=0.009, respectively). In contrast, the QTc interval at the time of myocarditis (435±39 ms) was not increased compared with pre-myocarditis baseline (422±27 ms, p=0.42). A prolonged QRS duration conferred an increased risk of subsequent MACE (HR 3.28, 95% CI 1.98 to 5.62, p<0.001). After adjustment, each 10 ms increase in the QRS duration conferred a 1.3-fold increase in the odds of MACE (95% CI 1.07 to 1.61, p=0.011). Conversely, there was no association between the QTc interval and MACE among men (HR 1.33, 95% CI 0.70 to 2.53, p=0.38) or women (HR 1.48, 95% CI 0.61 to 3.58, p=0.39). CONCLUSIONS: The QRS duration is increased in ICI myocarditis and is associated with increased MACE risk. Use of this widely available ECG parameter may aid in ICI myocarditis diagnosis and risk-stratification.

Understanding the Etiology of Adolescent Substance Use through Developmental Perspectives.

There are notable risks associated with alcohol, cigarette, and marijuana use during adolescence. Yet, there is no single cause for adolescent substance use. The etiology of substance use is known to develop over time, across multiple levels of influence. Informed by developmental perspectives, this review aims to provide an overview of biological (e.g., genetic, neuroimaging), individual (e.g., temperament, behavior problems), and social (e.g., parents, peers) factors that increase risk for and protection against this multifaceted phenomenon. Additionally, emerging areas of research are highlighted, as well as preliminary work examining the etiology of adolescent substance use across multiple levels of influence. Understanding early factors associated with the emergence of adolescent substance use can help inform prevention programming to reduce subsequent cognitive impairments and psychopathology. Adaptive individualized interventions addressing various domains linked to adolescent substance use in real-time are likely to have significant utility given the numerous pathways to adolescent substance use.

Associations Between Transdiagnostic Cognitive-Affective Vulnerability Factors, Negative Reinforcement Drinking Motives, and Problematic Alcohol Use among Undergraduates.

OBJECTIVE: Anxiety sensitivity, distress tolerance, and emotion regulation difficulties have each demonstrated significant individual associations with problematic alcohol use and negative reinforcement motives for alcohol use among college students. However, extant research has yet to examine these three factors simultaneously with regard to the possibility of differential associations with alcohol consumption, alcohol-related problems and coping and conformity motives for alcohol use. As such, the present study sought to examine whether such differential associations exist within a sample of undergraduates reporting past year alcohol use. Methods: Participants were 379 undergraduate students reporting alcohol use in the past year who completed self-report measures for course credit. Results: After controlling for the effects of sex, lifetime marijuana use status, and negative affectivity, greater anxiety sensitivity social concerns and difficulties with emotional awareness were associated with more alcohol-related problems. Greater anxiety sensitivity social concerns and impulse control difficulties were associated with greater conformity alcohol use motives, and greater impulse control and emotional clarity difficulties were associated with greater coping motives. Conclusions: These findings suggest that greater fears of anxiety symptoms because of their potential negative social consequences and certain emotion regulation difficulties (i.e., impulse control, emotional clarity, emotional awareness) may be particularly problematic because they are associated with alcohol-related problems and negative reinforcement motives for use among undergraduates.

Decreased Absolute Lymphocyte Count and Increased Neutrophil/Lymphocyte Ratio With Immune Checkpoint Inhibitor-Associated Myocarditis.

Background Myocarditis attributable to immune checkpoint inhibitor (ICI) therapy is a potentially fatal immune-related adverse event. Limited data have suggested an association between baseline and on-treatment absolute lymphocyte count (ALC) and neutrophil/lymphocyte ratio (NLR) and the development of other immune-related adverse events; there are no data characterizing the role of ALC and NLR in ICI-associated myocarditis. Methods and Results This was a case control study of 55 patients with ICI myocarditis and 55 controls without any post-ICI immune-related adverse events. We leveraged clinical testing, where patients underwent routine serial blood counts before and with each ICI cycle to compare the baseline and change in ALC and NLR between cases and controls. The association between the change in these parameters with clinical variables and major adverse cardiac events was also tested. In cases, there was a statistically significant decrease in ALC with myocarditis from baseline (1.6 thousands per cubic milliliter (K/µL); interquartile range, 1.1-1.9 K/µL) to admission (1.1 K/µL; interquartile range, 0.7-1.3 K/µL; P<0.001). Similarly, there was an increase in NLR from baseline (3.5; interquartile range, 2.3-5.4) to admission (6.6; interquartile range, 4.5-14.1; P<0.001). There was no statistically significant change in controls. In follow-up, there were 20 events; larger decreases in ALC (44.6% versus 18.2%; P<0.001) or increases in NLR (156.5% versus 65.1%; P=0.019) were associated with major adverse cardiac events. Conclusions A reduction in ALC and an increase in NLR was seen with ICI myocarditis. A greater decrease in ALC or increase in NLR was associated with subsequent major adverse cardiac events.