Outcomes of Emergency Department Patients With Opioid Use Disorder Utilizing a Virtual Addiction Bridge Clinic: A Case Series.

OBJECTIVES: Within the last decade, there has been a dramatic increase in the rate of emergency department (ED) visits and death from opioid overdose. Those who present to the ED are at high risk for subsequent morbidity and mortality. Despite effective treatment, many patients do not get rapidly connected to outpatient care. The aim of this investigation was to describe outpatient treatment engagement after ED discharge among patients with opioid use disorder (OUD) enrolled in a virtual Addiction Bridge Clinic (ABC). METHODS: This was a retrospective case series describing an ED-initiated referral for rapid telehealth follow-up among patients with OUD. The primary outcome was addiction treatment engagement among those who completed the initial virtual ABC visit (engaged in ABC) vs. those who did not complete an ABC visit (Not engaged in ABC) at 1 week, 1 month, and 3 and 6 months timepoint intervals after the initial ED presentation. RESULTS: Of the N = 201 patients referred to the ABC between March and December 2021, a majority were Black (71%) and male (77%). Of the 201 referrals, 85 (42%) completed an initial ABC telehealth visit. Subsequent treatment engagement was 26% at 1 week, 26% at 1 month, 22% at 3 months, and 18% at 6 months after the index ED visit. CONCLUSIONS: A telehealth-enabled virtual addiction bridge clinic is one potential approach to reduce barriers to rapid treatment access. Strategies are needed to improve subsequent addiction treatment engagement after a virtual addiction bridge clinic visit.

Behavioral and neurocognitive factors distinguishing post-traumatic stress comorbidity in substance use disorders.

Significant trauma histories and post-traumatic stress disorder (PTSD) are common in persons with substance use disorders (SUD) and often associate with increased SUD severity and poorer response to SUD treatment. As such, this sub-population has been associated with unique risk factors and treatment needs. Understanding the distinct etiological profile of persons with co-occurring SUD and PTSD is therefore crucial for advancing our knowledge of underlying mechanisms and the development of precision treatments. To this end, we employed supervised machine learning algorithms to interrogate the responses of 160 participants with SUD on the multidimensional NIDA Phenotyping Assessment Battery. Significant PTSD symptomatology was correctly predicted in 75% of participants (sensitivity: 80%; specificity: 72.22%) using a classification-based model based on anxiety and depressive symptoms, perseverative thinking styles, and interoceptive awareness. A regression-based machine learning model also utilized similar predictors, but failed to accurately predict severity of PTSD symptoms. These data indicate that even in a population already characterized by elevated negative affect (individuals with SUD), especially severe negative affect was predictive of PTSD symptomatology. In a follow-up analysis of a subset of 102 participants who also completed neurocognitive tasks, comorbidity status was correctly predicted in 86.67% of participants (sensitivity: 91.67%; specificity: 66.67%) based on depressive symptoms and fear-related attentional bias. However, a regression-based analysis did not identify fear-related attentional bias as a splitting factor, but instead split and categorized the sample based on indices of aggression, metacognition, distress tolerance, and interoceptive awareness. These data indicate that within a population of individuals with SUD, aberrations in tolerating and regulating aversive internal experiences may also characterize those with significant trauma histories, akin to findings in persons with anxiety without SUD. The results also highlight the need for further research on PTSD-SUD comorbidity that includes additional comparison groups (i.e., persons with only PTSD), captures additional comorbid diagnoses that may influence the PTSD-SUD relationship, examines additional types of SUDs (e.g., alcohol use disorder), and differentiates between subtypes of PTSD.

Development and clinical feasibility study of a brief version of an addiction-focused phenotyping battery in females receiving buprenorphine for opioid use disorder.

INTRODUCTION: We aimed to streamline the NIDA Phenotyping Assessment Battery (PhAB), a package of self-report scales and neurobehavioral tasks used in substance use disorder (SUD) clinical trials, for clinical administration ease. Tailoring the PhAB to shorten administration time for a treatment setting is critical to expanding its acceptability in SUD clinical trials. This study's primary objectives were to develop a brief version of PhAB (PhAB-B) and assess its operational feasibility and acceptability in a female clinical treatment sample. METHODS: Assessments of the original PhAB were evaluated along several criteria to identify a subset for the PhAB-B. Non-pregnant females (N=55) between ages 18-65, stabilized on buprenorphine for opioid use disorder (OUD) at an outpatient addiction clinic, completed this abbreviated battery remotely or after a provider visit in clinic. Participant satisfaction questions were administered. REDCap recorded the time to complete PhAB-B measures. RESULTS: The PhAB-B included 11 measures that probed reward, cognition, negative emotionality, interoception, metacognition, and sleep. Participants who completed the PhAB-B (N =55) were 36.1 ± 8.9 years of age, White (54.5%), Black (34.5%), and non-Latinx (96.0%). Most participants completed the PhAB-B remotely (n = 42, 76.4%). Some participants completed it in-person (n = 13, 23.6%). PhAB-B mean completion time was 23.0 ± 12.0 min. Participant experiences were positive, and 96% of whom reported that they would participate in the study again. CONCLUSION: Our findings support the clinical feasibility and acceptability of the PhAB-B among a female opioid use disorder outpatient addiction treatment sample. Future studies should assess the PhAB-B psychometric properties among broader treatment samples.

Rapid induction onto extended-release injectable buprenorphine following opioid overdose: A case series.

Background: Buprenorphine treatment has been associated with reduced non-prescribed opioid use and opioid related overdose (OD). We evaluated initial outcomes of rapid induction onto extended-release injectable buprenorphine (BUP-XR) within 7 days of emergency department presentation for unintentional OD. Methods: Between February 2019-February 2021, N = 19 patients with opioid use disorder received buprenorphine/naloxone (4/1 mg), followed by BUP-XR (300 mg) at induction and continued BUP-XR outpatient for 6 months. Primary outcomes included adverse events, repeat OD, and death. Results: For patients who received at least one dose of BUP-XR, there were no treatment related serious adverse events or symptoms of precipitated withdrawal. In addition, there were no repeat visits for ODs or deaths within 6 months of the initial OD. Discussion: These preliminary findings support the need for larger controlled clinical trials to examine the safety and efficacy of rapid induction of BUP-XR in patients with opioid use disorder at high risk of opioid OD. Rapid induction onto long-lasting injectable buprenorphine may be a promising and protective treatment approach in the future.

New approaches to deep phenotyping in addictions.

OBJECTIVE: The causes of substance use disorders (SUDs) are largely unknown and the effectiveness of their treatments is limited. One crucial impediment to research and treatment progress surrounds how SUDs are classified and diagnosed. Given the substantial heterogeneity among individuals diagnosed with a given SUD (e.g., alcohol use disorder [AUD]), identifying novel research and treatment targets and developing new study designs is daunting. METHOD: In this article, we review and integrate two recently developed frameworks, the National Institute on Drug Abuse's Phenotyping Assessment Battery (NIDA PhAB) and the Hierarchical Taxonomy of Psychopathology (HiTOP), that hope to accelerate progress in understanding the causes and consequences of psychopathology by means of deep phenotyping, or finer-grained analysis of phenotypes. RESULTS AND CONCLUSIONS: NIDA PhAB focuses on addiction-related processes across multiple units of analysis, whereas HiTOP focuses on clinical phenotypes and covers a broader range of psychopathology. We highlight that NIDA PhAB and HiTOP together provide deep and broad characterizations of people diagnosed with SUDs and complement each other in their efforts to address widely known limitations of traditional classification systems and their diagnostic categories. Next, we show how NIDA PhAB and HiTOP can be integrated to facilitate optimal rich phenotyping of addiction-related phenomena. Finally, we argue that such deep phenotyping promises to advance our understanding of the neurobiology of SUD and addiction, which will guide the development of personalized medicine and interventions. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Initial Validation of a Behavioral Phenotyping Model for Substance Use Disorder.

Standard nosological systems, such as DSM-5 or ICD-10, are relied upon as the diagnostic basis when developing treatments for individuals with substance use disorder (SUD). Unfortunately, the vast heterogeneity of individuals within a given SUD diagnosis results in a variable treatment response and/or difficulties ascertaining the efficacy signal in clinical trials of drug development. Emerging precision medicine methods focusing on targeted treatments based on phenotypic subtypes rather than diagnosis are being explored as alternatives. The goal of the present study was to provide initial validation of emergent subtypes identified by an addiction-focused phenotyping battery. Secondary data collected as part of a feasibility study of the NIDA phenotyping battery were utilized. Participants completed self-report measures and behavioral tasks across six neurofunctional domains. Exploratory and confirmatory factor analysis (EFA/CFA) were conducted. A three-factor model consisting of negative emotionality, attention/concentration, and interoception and mindfulness, as well as a four-factor model adding a second negative emotion domain, emerged from the EFA as candidate models. The CFA of these models did not result in a good fit, possibly resulting from small sample sizes that hindered statistical power.

Sex Specific Sleep Parameters Among People With Substance Use Disorder.

Introduction: Sleep can have substantial impacts in substance use disorder (SUD) pathogenesis, treatment, and recovery. Sex differences exist in both sleep and SUD, but how sleep is uniquely associated with SUD by sex is not known. The study objective was to compare, within sex, sleep parameters between individuals with SUD and non-substance misusing controls. Methods: Secondary analyses of a parent cross-sectional study examining the feasibility and acceptability of a novel neurocognitive phenotyping assessment battery were completed. SUD and control subjects were recruited through local advertising and an established research registry. Subjects with SUD were also recruited through a university-based outpatient SUD treatment clinic. Self-reported sleep quality was assessed using the Pittsburgh Sleep Quality Index (PSQI). Sex-stratified t-tests compared sleep between SUD and control subjects while Crosstab analyses explored group differences in the proportion of individuals reporting poor sleep (defined as PSQI ≥ 5). Results: Data from 162 males (44 controls, 118 SUD) and 146 females (64 controls, 82 SUD) were included in the present study. For females only, a significantly lower proportion of controls reported PSQI-defined poor sleep than individuals with any SUD or specifically with opioid use disorder. Male, but not female, controls reported shorter sleep latency, longer sleep duration, and less sleep disturbance than males with each SUD type. Discussion/Implications: Sleep holds promise as an avenue to address SUD within a biopsychosocial model. Future work at the intersection of SUD and sleep should prioritize investigations of their interplay with sex to identify targets for tailored SUD interventions.

Attentional function and inhibitory control in different substance use disorders.

Attentional function in substance use disorder (SUD) is not well understood. To probe attentional function in SUD as a function of primary substance of abuse, we administered the attentional network task (ANT) to 44 individuals with Cocaine Use Disorder (CoUD), 49 individuals with Cannabis Use Disorder (CaUD), 86 individuals with Opioid Use Disorder (OUD), and 107 controls with no SUD, along with the stop-signal task (SST). The ANT quantifies the effects of (temporal) alerting cues and (spatial) orienting cues to reduce reaction time (RT) to targets, as well as probing how conflicting (target-incongruent) stimuli slow RT. The SST quantifies individuals' ability to inhibit already-initiated motor responses. After controlling for sex representation and age, OUD and CaUD participants showed blunted alerting effects compared to controls, whereas CaUD and CoUD participants showed greater stimulus conflict (flanker) effects. Finally, CoUD participants showed a trend toward increased orienting ability. In SST performance, no SUD group showed a prolonged stop-signal reaction compared to controls. However, the OUD group (and CoUD group at trend level) showed prolonged "go" RT to targets and reduced hit rates. These data indicate differences in attentional function in persons with SUD as a function of the primary substance use.

Improving Peripartum Care Engagement Among Black Women at Risk for Low Prenatal Care Attendance: A Secondary Analysis of Predictors of Attendance and Sample Representativeness.

Background: The United States has unacceptably high rates of maternal and infant mortality, especially among Black women and their infants. Prenatal and postpartum care help reduce maternal and infant morbidity and mortality; however, Black women are less likely to access and utilize peripartum care largely due to structural racism. Identifying factors that buffer against the systemic barriers disproportionately impacting this community is an important step in addressing racial health disparities. Using existing data from a randomized controlled trial (RCT) targeting maternal and infant health disparities, this study aims to (1) explore predictors of peripartum care attendance and (2) examine clinical trial sample representativeness. Methods: The analyses addressing the primary aim of the study included Black women at risk for low prenatal care (PNC) engagement who consented to RCT participation and had a documented live birth (n = 123). For the secondary study aim, comparisons between women who consented to the RCT (Consenters; n = 149) and those who did not (Non-consenters; n = 122) were made using chi-square and t-tests. Results: Hierarchical linear and logistic regression identified predictors of prenatal and postpartum care attendance, respectively. After controlling for multiple comparisons, no significant differences were identified between characteristics of Consenters and Non-consenters. Older age (p = 0.038), high-risk pregnancy (p < 0.001), and no past week substance use (p = 0.033) predicted better PNC attendance. PNC attendance predicted postpartum visit attendance (p < 0.001). Conclusions: This study provides benchmark data on predictors of peripartum care and sample representativeness in RCTs. Findings have important implications for health care system changes and development of culturally informed interventions.

Increasing Prenatal Care Compliance in At-Risk Black Women: Findings from a RCT of Patient Navigation and Behavioral Incentives.

BACKGROUND: In the USA, infant mortality remains a major public health concern, particularly for Black women and their infants who continue to experience disproportionately high mortality rates. Prenatal care is a key determinant of infant health, with inadequate prenatal care increasing risk for prematurity, stillbirth, neonatal loss, and infant death. The aim of the present study was to determine if concurrent delivery of patient navigation and behavioral incentives to at-risk Black pregnant women could improve prenatal care attendance and associated maternal and infant outcomes. METHODS: Participants were 150 Black pregnant women recruited at first prenatal visit and screening at risk for adverse maternal and infant outcomes. Women were randomized to either the patient navigation + behavioral incentives intervention (PNBI) or assessment + standard care control (ASC) group. All were followed throughout pregnancy and 12-week postpartum. Group comparisons were made using intention-to-treat and per-protocol sensitivity analyses. RESULTS: While no group differences were found in prenatal care visits, the average number of visits for both groups (9.3 for PNBI and 8.9 for ASC) approached the American College of Obstetricians and Gynecologists (ACOG) recommended guidelines. There were also no group differences in maternal and infant outcomes. Both intention-to-treat and per-protocol sensitivity analyses, however, consistently found PNBI women attended more postpartum visits than ASC controls (p = 0.002). CONCLUSIONS: Given ACOG's redefining of the postpartum period as the fourth trimester, study findings suggest PNBI may facilitate prevention and intervention efforts to more successfully reduce health disparities in outcomes for both mother and infant.

Safety and Preliminary Efficacy of Lorcaserin for Cocaine Use Disorder: A Phase I Randomized Clinical Trial.

Background and Objectives: Preclinical studies show serotonin (5-HT) 5-HT2C receptor (5-HT2CR) agonists reduce cocaine-seeking and cocaine intake. This study examined safety of the 5-HT2CR agonist lorcaserin administered with cocaine in participants with cocaine use disorder (CocUD). Secondarily, subjective response to cocaine and choice of cocaine vs. money were examined. Methods: A double-blind, randomized, placebo-controlled trial of 25 inpatient non-treatment seeking participants with CocUD. Participants were randomized to either lorcaserin (n = 17) or placebo (n = 8). Primary outcome measures included cardiovascular measures and plasma cocaine levels. Secondary measures of subjective response to cocaine were assessed using a visual analog scale (VAS) and cocaine vs. money progressive ratio choice sessions. Results: Thirteen randomized participants were included in the final analysis. No serious or unexpected adverse events were related to lorcaserin. There were no significant interactions between cocaine and lorcaserin on cardiovascular measures, plasma cocaine, or subjective ratings. After multiple comparisons correction, cocaine significantly increased blood pressure, heart rate, and QTc. Lorcaserin significantly decreased VAS ratings of "feel irritable," "feel hungry," and "I am craving." For the cocaine vs. money choice procedure, there was a significant interaction between choice (cocaine vs. money) and lorcaserin. Participants treated with lorcaserin were more likely to choose cocaine. Discussion and Conclusions: This study showed safety of lorcaserin administered with cocaine but lack of efficacy to reduce the reinforcing effects of cocaine. Scientific Significance: This study is the first to show a disconnect between effects of 5-HT2CR agonists on craving and cocaine choice in human cocaine users.

Social Information Processing in Substance Use Disorders: Insights From an Emotional Go-Nogo Task.

Positive social connections are crucial for recovery from Substance Use Disorder (SUD). Of interest is understanding potential social information processing (SIP) mediators of this effect. To explore whether persons with different SUD show idiosyncratic biases toward social signals, we administered an emotional go-nogo task (EGNG) to 31 individuals with Cocaine Use Disorder (CoUD), 31 with Cannabis Use Disorder (CaUD), 79 with Opioid Use Disorder (OUD), and 58 controls. Participants were instructed to respond to emotional faces (Fear/Happy) but withhold responses to expressionless faces in two task blocks, with the reverse instruction in the other two blocks. Emotional faces as non-targets elicited more "false alarm" (FA) commission errors as a main effect. Groups did not differ in overall rates of hits (correct responses to target faces), but participants with CaUD and CoUD showed reduced rates of hits (relative to controls) when expressionless faces were targets. OUD participants had worse hit rates [and slower reaction times (RT)] when fearful faces (but not happy faces) were targets. CaUD participants were most affected by instruction effects (respond/"go" vs withhold response/"no-go" to emotional face) on discriminability statistic A. Participants were faster to respond to happy face targets than to expressionless faces. However, this pattern was reversed in fearful face blocks in OUD and CoUD participants. This experiment replicated previous findings of the greater salience of expressive face images, and extends this finding to SUD, where persons with CaUD may show even greater bias toward emotional faces. Conversely, OUD participants showed idiosyncratic behavior in response to fearful faces suggestive of increased attentional disruption by fear. These data suggest a mechanism by which positive social signals may contribute to recovery.

Development and Feasibility Study of an Addiction-Focused Phenotyping Assessment Battery.

BACKGROUND AND OBJECTIVES: Current methods of classifying individuals with substance use disorder (SUD) result in vast heterogeneity among persons within a given diagnosis. These approaches, while clinically allowing for distinctions between patient groups, are less than ideal when attempting to recruit a neurobehaviorally defined subset of subjects into clinical trials. To address this gap, alternative strategies have been proposed, including behavioral phenotyping. The NIDA Phenotyping Assessment Battery (PhAB) is a modular package of assessments and neurocognitive tasks that was developed for use in clinical trials. The goal of the present study is to assess the feasibility of the NIDA PhAB with regard to ease of administration and time burden. METHODS: Healthy controls, persons with cocaine use disorder (CocUD), opioid use disorder (OUD), cannabis use disorder (CanUD), and combined opioid and cocaine use disorder (OCUD) were recruited from various sources (N = 595). Participants completed screening and one to three assessment visits. Time to complete the measures was recorded and a satisfaction interview was administered. RESULTS: Of the participants enrolled, 381 were deemed eligible. The majority of eligible participants (83%) completed all assessments. The average completion time was 3 hours. High participant satisfaction ratings were noted, with over 90% of participants endorsing a willingness to participate in a similar study and recommend the study to others. CONCLUSION AND SCIENTIFIC SIGNIFICANCE: These findings corroborate the ease with which the PhAB may be easily incorporated into a study assessment visit without undue participant burden. The PhAB is an efficient method for behavioral phenotyping in addiction clinical trials. (Am J Addict 2021;00:00-00).

Clinical features and outcomes between African American and Caucasian patients with Takotsubo Syndrome.

BACKGROUND: Takotsubo syndrome (TS) is an acute, reversible form of heart failure, often mimicking an acute coronary syndrome (ACS). Data regarding racial differences in TS are inconsistent. The aim is to assess clinical features associated with unfavorable in-hospital outcomes between African American (AA) and Caucasian (CAU) patients. METHODS: A retrospective electronic health record query identified 44 AA patients and 110 CAU patients with a diagnosis of TS. Our primary outcome was a composite of death, stroke, and cardiogenic shock during hospitalization. Variables associated with an increased risk of the primary composite outcomes were included in a logistic regression model. RESULTS: Compared to CAU patients, AA patients were a more comorbid population, and presented a higher prevalence of history of illicit drug use (27.3% vs. 13.6% P=0.044). There were no significant differences regarding in-hospital complication rates between AA and CAU patients. In the logistic regression model, infection was associated with greater risk of developing the primary outcome in AA patients (OR=7.26 [95% CI 1.22-43.17], P=0.029), whereas angina was a protective factor (OR=0.11 [95% CI 0.02-0.65], P=0.015). In CAU patients, severely depressed ejection fraction and worse peak creatinine during hospitalization increased risk of developing the primary outcome (OR=5.88 95% CI [2.01-17.17], P<0.001 and OR=1.64 [95% CI 1.15-2.58], P=0.031, respectively). Meanwhile, emotional stressors were protective (OR=0.16 [95% CI 0.03-0.88], P=0.004). CONCLUSIONS: Despite experiencing the same rate of in-hospital complications, the clinical profiles of AA patients are distinct from CAU patients admitted for TS, and clinical variables correlated with worse in-hospital outcomes also differ by race.

Resting-State Directional Connectivity and Anxiety and Depression Symptoms in Adult Cannabis Users.

BACKGROUND: Anxiety and depression symptoms are common among cannabis users and could be a risk factor for cannabis use (CU) disorder. Thus, it is critical to understand the neuronal circuits underlying the associations between CU and these symptoms. Alterations in resting-state functional connectivity within and/or between the default mode network and salience network have been reported in CU, anxiety, and depressive disorders and thus could be a mechanism underlying the associations between CU disorder and anxiety/depression symptoms. METHODS: Using resting-state functional magnetic resonance imaging, effective connectivities (ECs) among 9 major nodes from the default mode network and salience network were measured using dynamic causal modeling in 2 datasets: the Human Connectome Project (28 CU participants and 28 matched non-drug-using control participants) and a local CU study (21 CU participants and 21 matched non-drug-using control participants) in separate and parallel analyses. RESULTS: Relative to the control participants, right amygdala to left amygdala, anterior cingulate cortex to left amygdala, and medial prefrontal cortex to right insula ECs were greater, and left insula to left amygdala EC was smaller in the CU group. Each of these ECs showed a reliable linear relationship with at least one of the anxiety/depression measures. Most findings on the right amygdala to left amygdala EC were common to both datasets. CONCLUSIONS: Right amygdala to left amygdala and anterior cingulate cortex to left amygdala ECs may be related to the close associations between CU and anxiety/depression symptoms. The findings on the medial prefrontal cortex to right insula and left insula to left amygdala ECs may reflect a compensatory mechanism.

Preliminary Findings of Weaker Executive Control Network Resting State fMRI Functional Connectivity in Opioid Use Disorder compared to Healthy Controls.

Objective: Resting state functional magnetic resonance imaging (fMRI) functional connectivity has been used as a tool to study brain mechanisms associated with addictions. Recent research in substance use disorders has focused on three brain networks termed the default mode network (DMN), salience network (SN), and executive control network (ECN). The purpose of this study was to examine the functional connectivity of those three networks in opioid use disorder (OUD) subjects compared to healthy control subjects (HC). Methods: The present study investigated functional connectivity differences between OUD subjects compared to HC using independent component analysis. This study also examined the relationship between functional connectivity and negative urgency scores, as well as compared the functional connectivity of severe OUD to mild or moderate OUD. Results: In OUD subjects (n=25) compared to HC (n=25), a cluster in the left dorsolateral prefrontal cortex within the left ECN had significantly weaker functional connectivity. No significant differences were found between groups for the functional connectivity of the DMN, SN, or right ECN. No significant associations were found between functional connectivity and negative urgency, and no differences were found between severe OUD and mild or moderate OUD. Conclusion: These novel preliminary results suggest that ECN functional connectivity may differ between OUD and HC. This finding is consistent with previous research showing altered executive function in OUD and supports further examination of ECN functional connectivity in association with treatment response in OUD. Given our relatively small sample size (50 subjects total; 25 subjects per group), our results should be treated as preliminary for hypothesis generation, and replication will be needed in future studies.

Feasibility of bystander-administered naloxone delivered by drone to opioid overdose victims.

BACKGROUND: Currently, ≤5% of bystanders witnessing an opioid overdose (OD) in the US administer antidote to the victim. A possible model to mitigate this crisis would be a system that enables 9-1-1 dispatchers to both rapidly deliver naloxone by drone to bystanders at a suspected opioid OD and direct them to administer it while awaiting EMS arrival. METHODS: A simulated 9-1-1 dispatcher directed thirty subjects via 2-way radio to retrieve naloxone nasal spray from atop a drone located outside the simulation building and then administer it using scripted instructions. The primary outcome measure was time from first contact with the dispatcher to administration of the medication. RESULTS: All subjects administered the medication successfully. The mean time interval from 9 -1-1 contact until antidote administration was 122 [95%CI 109-134] sec. There was a significant reduction in time interval if subjects had prior medical training (p = 0.045) or had prior experience with use of a nasal spray device (p = 0.030). Five subjects had difficulty using the nasal spray and four subjects had minor physical impairments, but these barriers did not result in a significant difference in time to administration (p = 0.467, p = 0.30). A significant number of subjects (29/30 [97%], p = 0.044) indicated that they felt confident they could administer intranasal naloxone to an opioid OD victim after participating in the simulation. CONCLUSIONS: Our results suggest that bystanders can carry out 9-1-1 dispatcher instructions to fetch drone-delivered naloxone and potentially decrease the time interval to intranasal administration which supports further development and testing of a such a system.

Tobacco smoke exposure as a risk factor for human papillomavirus infections in women 18-26 years old in the United States.

BACKGROUND: Although tobacco smoke has been associated with many infections, little is known of its association with human papillomavirus (HPV) infections among young adult women. The aim of the study was to explore the association of tobacco smoke exposure on HPV infections in young adult women in the United States. It was hypothesized that tobacco smoke exposure (both active and passive) as objectively measured by cotinine levels was associated with increased HPV infection in a national sample of 18 and 26 year-old women in the United States. STUDY METHODS AND FINDINGS: The NHANES 2007-2012 dataset was used in the analyses. A national representative sample of women 18 to 26 year old (N = 1,414) was included in the study. Infection with any HPV was determined by PCR while tobacco smoke exposure was determined by measuring serum cotinine levels. Women with cotinine levels <0.05 ng/mL were considered unexposed and those with levels > = 0.05 were considered as exposed. Exposed women were further categorized as passive smokers (cotinine levels 0.05-<10 ng/mL, while active smokers were those with cotinine levels = > 10ng/mL). Data were analyzed by descriptive statistics and multiple logistic regression analysis. Exposed women (passive smokers with cotinine levels > = 0.05ng/mL-10ng/mL) were almost 2 times (64% vs 35%) more likely to be infected with any HPV type than their unexposed counterparts (cotinine levels <0.05ng/mL). Also women who were active smokers (cotinine levels > = 10 ng/mL) were more than twice more likely (75%) to be infected with the virus than the unexposed counterparts. The relationship held true even after controlling for various socio-demographics. Indeed in the multiple regression analyses controlling for the various confounders, compared to their unexposed counterparts, women exposed to second hand smoke were more than twice more likely to have HPV infections (OR: 2.45; 95% C.I = 1.34-4.48). When compared to their unexposed counterparts, actively smoking women were more than 3.5 times more likely to be infected with HPV (OR = 3.56; 95% CI 1.23-10.30). Finally, a strong dose-response relationship was further demonstrated with increasing risk of HPV with each quartile of cotinine levels even after controlling for various confounders. The risk of HPV was lowest in the lowest quartile (Referent OR = 1) and increased steadily with each quartile of cotinine levels until the risk was highest among women with cotinine levels in the 4th quartile (OR = 4.16; 95% C.I. = 1.36-12.67). CONCLUSION: Both passive and active tobacco smoking were strongly associated with any HPV infection in 18 to 26 year old young women with a significant dose-response relationship. Future studies should explore the effect of tobacco smoke exposure among younger women less than 18 years of age.

Stress Cardiomyopathy Diagnosis and Treatment: JACC State-of-the-Art Review.

Stress cardiomyopathy is an acute reversible heart failure syndrome initially believed to represent a benign condition due to its self-limiting clinical course, but now recognized to be associated with a non-negligible rate of serious complications such as ventricular arrhythmias, systemic thromboembolism, and cardiogenic shock. Due to an increased awareness and recognition, the incidence of stress cardiomyopathy has been rising (15-30 cases per 100,000 per year), although the true incidence is unknown as the condition is likely underdiagnosed. Stress cardiomyopathy represents a form of neurocardiogenic myocardial stunning, and while the link between the brain and the heart is established, the exact pathophysiological mechanisms remain unclear. We herein review the proposed risk factors and triggers for the syndrome and discuss a practical approach to diagnosis and treatment of the patients with stress cardiomyopathy, highlighting potential challenges and unresolved questions.

Fronto-striatal effective connectivity of working memory in adults with cannabis use disorder.

Previous working memory (WM) studies found that relative to controls, subjects with cannabis use disorder (CUD) showed greater brain activation in some regions (e.g., left [L] and right [R] ventrolateral prefrontal cortex [VLPFC], and L dorsolateral prefrontal cortex [L-DLPFC]), and lower activation in other regions (e.g., R-DLPFC). In this study, effective connectivity (EC) analysis was applied to functional magnetic resonance imaging data acquired from 23 CUD subjects and 23 controls (two groups matched for sociodemographic factors and substance use history) while performing an n-back WM task with interleaved 2-back and 0-back periods. A 2-back minus 0-back modulator was defined to measure the modulatory changes of EC corresponding to the 2-back relative to 0-back conditions. Compared to the controls, the CUD group showed smaller modulatory change in the R-DLPFC to L-caudate pathway, and greater modulatory changes in L-DLPFC to L-caudate, R-DLPFC to R-caudate, and R-VLPFC to L-caudate pathways. Based on previous fMRI studies consistently suggesting that greater brain activations are related to a compensatory mechanism for cannabis neural effects (less regional brain activations), the smaller modulatory change in the R-DLPFC to L-caudate EC may be compensated by the larger modulatory changes in the other prefrontal-striatal ECs in the CUD individuals.