Safety and tolerability of topiramate and N-acetyl cysteine combination in individuals with alcohol use disorder: a 12 week, randomized, double-blind, pilot study.

Topiramate (TPM), a GABA/glutamate modulator, has shown positive results for treating alcohol use disorder (AUD), but causes significant cognitive adverse effects. TPM causes cognitive side effects by reducing glutathione levels in the frontal lobe. N-acetyl cysteine (NAC) increases level of intracellular glutathione. We hypothesized that combining NAC with TPM may mitigate the possible cognitive side effects of TPM, as well as working synergistically in reducing alcohol consumption more efficaciously than using TPM alone. A 12-week, double-blind randomized trial assessing the effects of combining NAC (1200 mg/day) with TPM (200 mg/day) vs TPM alone (i) cognitive side effects caused by TPM, (ii) percentage of heavy drinking days (PHDD) and percentage of days abstinent (PDA) using weekly calendar, and (iii) craving outcomes using the obsessive-compulsive drinking scale. Seventeen participants were randomized into the study (nine received TPM + NAC and eight matching TPM + Placebo). Cognitive adverse events were not significantly different between the treatment arms (P = 0.581). There was no difference in PHDD (P = 0.536) and in PDA over the entire study period (P = 0.892). However, both treatment groups at study end, compared with the baseline, significantly reduced their PHDD and increased their PDA. As for cravings: TPM + NAC group has shown higher level in automaticity of drinking (P = 0.029) and interference due to drinking (P = 0.014) subscales compared with the TPM + Placebo group. No difference was observed between groups in terms of Drinking Obsessions and Alcohol Consumption subscales. This pilot study indicates that combining NAC with TPM is overall safe, but the addition of NAC has no significant benefit over placebo in the incidence of TPM-related cognitive impairment, and alcohol drinking. Furthermore, craving outcomes may become worse with the addition of NAC.

Impact of Medicaid Expansion on Abdominal Surgery Morbidity, Mortality, and Hospital Readmission.

INTRODUCTION: Medicaid expansion's (ME) impact on postoperative outcomes after abdominal surgery remains poorly defined. We aimed to evaluate ME's effect on surgical morbidity, mortality, and readmissions in a state that expanded Medicaid (Virginia) compared to a state that did not (Tennessee) over the same time period. METHODS: Virginia Surgical Quality Collaborative (VSQC) American College of Surgeons National Surgical Quality Improvement Program data for Medicaid, uninsured, and private insurance patients undergoing abdominal procedures before Virginia's ME (3/22/18-12/31/18) were compared with post-ME (1/1/19-12/31/19), as were corresponding non-ME state Tennessee Surgical Quality Collaborative (TSQC) data for the same 2018 and 2019 time periods. Postexpansion odds ratios for 30-d morbidity, 30-d mortality, and 30-d unplanned readmission were estimated using propensity score-adjusted logistic regression models. RESULTS: In Virginia, 4753 abdominal procedures, 2097 pre-ME were compared to 2656 post-ME. In Tennessee, 5956 procedures, 2484 in 2018 were compared to 3472 in 2019. VSQC's proportion of Medicaid population increased following ME (8.9% versus 18.8%, P < 0.001) while uninsured patients decreased (20.4% versus 6.4%, P < 0.001). Post-ME VSQC had fewer 30-d readmissions (12.2% versus 6.0%, P = 0.013). Post-ME VSQC Medicaid patients had significantly lower probability of morbidity (-8.18, 95% confidence interval: -15.52 ∼ -0.84, P = 0.029) and readmission (-6.92, 95% confidence interval: -12.56 ∼ -1.27, P = 0.016) compared to pre-ME. There were no differences in probability of morbidity or readmission in the TSQC Medicaid population between study periods (both P > 0.05); there were no differences in mortality between study periods in VSQC and TSQC patient populations (both P > 0.05). CONCLUSIONS: ME was associated with decreased 30-d morbidity and unplanned readmissions in the VSQC. Data-driven policies accounting for ME benefits should be considered.

Examination of Tobacco-Related Messaging and Tobacco Use over Time among U.S. Military Young Adults.

Background: People from minoritized populations have historically been targeted by tobacco companies. Little is known about exposure to tobacco-related messages among military personnel from disadvantaged backgrounds. Objectives: The current study aimed to examine exposure to tobacco-related messaging across many nicotine products and through a variety of mediums (i.e., family, friends, advertisements, event promotions, social media) among diverse military populations and use one year later in a sample of young adults who recently enlisted in the U.S. Air Force. Methods: In this study, 8,901 U.S. Air Force trainees reported on demographics, tobacco use, and exposure to positive tobacco messages from social sources (i.e., friends, family, social media) and environmental sources (i.e., advertisements and promotions). Tobacco use was reported one-year later. Results: Compared to others of the same reported racial/ethnic background, Latino/a/x (Relative Risk Ratio [RRR] = 1.354, 95% CI: [1.145, 1.563]) and multiracial (RRR = 1.594, 95% CI: [1.173, 2.016]) participants who were exposed to positive tobacco messages from social sources were significantly more likely to report tobacco product use at one-year follow-up than those who were not exposed to social messages. Exposure to positive tobacco messages from environmental sources were not significantly associated with tobacco use one year later. Conclusions: Social messages may play an important role in increasing risk of tobacco use among some minoritized populations. Cultural as well as systemic factors could be addressed in future tobacco prevention programs to decrease the potency of positive tobacco-related social messages among Latino/a/x and multiracial communities.

Decreasing alcohol use among young adults presenting for service in the U.S. Air Force: An epidemiological surveillance study.

U.S. surveys demonstrate recent decreases in the prevalence of alcohol use and binge drinking among young adults. The current study aims to determine whether similar trends are evident in a similarly aged cohort of service members in the US Air Force to inform ongoing prevention efforts. Participants were 103,240 Air Force personnel in entry-level training between 2016 and 2019. Participants anonymously completed the AUDIT (Alcohol Use Disorder Identification Test) regarding their pre-service drinking. Logistic regression analyses and the Cochran-Armitage test were conducted to measure population trends over the study duration with stratification by age (<21 vs. ≥21) and evaluation of specific alcohol behaviors. Between 2016 and 2019, the proportion of young service members endorsing any alcohol use significantly decreased for both the <21 group (i.e. from 38.9% to 32.6%) and the ≥21 group (i.e. from 80.6% to 77.5%). Among those who endorsed drinking, a decrease over time in binge use was also observed from 46.6% to 37.8% for the <21 group and from 34.2% to 27.5% for the ≥21 group. Responses to other specific alcohol risk items and total AUDIT scores also demonstrated decreases. Binge use and risky drinking remained disproportionately common among those under the legal drinking age. It is encouraging to observe a shift toward abstinence and decreased binge use among this population of young military recruits. However, given the risk for many adverse health and legal consequences in this population, more work is needed to prevent problematic drinking, especially among those under the legal drinking age.

Validation of serotonin transporter mRNA as a quantitative biomarker of heavy drinking and its comparison to ethyl glucuronide/ethyl sulfate: A randomized, double-blind, crossover trial.

BACKGROUND: The serotonin transporter (SERT) mRNA was previously reported to be a quantitative and pathophysiology-based biomarker of heavy drinking in 5HTTLPR:LL genotype-carriers treated with ondansetron. Here, we validated the potential use of SERT mRNA for quantitative prediction of recent alcohol consumption (in the absence of treatment) and compared it with the known biomarkers ethyl glucuronide (EtG) and ethyl sulfate (EtS). METHODS: Binge drinking men and women of European ancestry aged 21 to 65 years were enrolled in a 12-day, in-patient, randomized, double-blind, crossover study, where they were administered three beverage doses (placebo, 0.5 g/kg [0.4 g/kg] ethanol, and 1 g/kg [0.9 g/kg] ethanol for men [women]) individually in three 4-day periods (experiments), separated by minimum 7-day washout period. Diet, sleep, and physical activity were controlled throughout the inpatient experiments. Twenty-nine participants were randomized to receive beverage doses counterbalancing the sequence of treatment and gender within subgroups stratified by SERT genotypes 5HTTLPR:LL+rs25531:AA (LA LA ) versus 5HTTLPR:LS/SS. Peripheral venous blood was collected daily for (1) quantification of SERT mRNA (the primary outcome measure) using qRT-PCR and (2) plasma EtG and EtS levels using tandem mass-spectrometry. RESULTS: The association between administered beverage dose and SERT mRNA from completers of at least one 4-day experiment (N = 18) assessed by a linear mixed model was not statistically significant. Significant positive associations were found with beverage dose and plasma EtG, EtS and EtG/EtS ratio (ß = 5.8, SE = 1.2, p < 0.0001; ß = 1.3, SE = 0.6, p = 0.023; and ß = 3.0, SE = 0.7, p < 0.0001, respectively; the C-statistics for discriminating outcomes were 0.97, 0.8, and 0.92, respectively). Additionally, we observed a sequence effect with a greater placebo effect on SERT mRNA when it was administered during the first experiment (p = 0.0009), but not on EtG/EtS measures. CONCLUSION: The findings do not validate the use of SERT as a biomarker of heavy drinking. Larger and more innovative studies addressing the effects of placebo, race, gender, and response to treatment with serotonergic agents are needed to fully assess the utility of SERT as a biomarker of heavy and binge drinking.

Trends in Tobacco Use among Young Adults Presenting for Military Service in the United States Air Force between 2013 and 2018.

Background: The US military has historically higher tobacco use compared to civilians, and tobacco use increases following enlistment. While the military is vulnerable to tobacco use, current surveillance of tobacco among this high-risk population is lacking. Methods: Recently enlisted Airmen (N = 43,597) between 2013 and 2018 were asked about tobacco use prior to enlistment across ten products: (1) cigarettes/roll your own tobacco, (2) smokeless tobacco/snus, (3) cigars, cigarillos/little cigars, (4) hookah/pipe, and (5) e-cigarettes. Results: Hookah/pipe use, cigarettes/roll your own, smokeless tobacco/snus, and cigars/little cigars/cigarillos use decreased significantly between 2013 and 2018, while the prevalence of e-cigarette use increased (p's < 0.0001). The relationships between the time and each tobacco product(s) use outcomes were influenced differently by different age, race, education and marital status. Conclusion: While e-cigarette use has increased in the civilian sector, the use of e-cigarettes among new recruits increased much more drastically (i.e. prevalence 15.3% in 2018). Further, demographic characteristics influenced tobacco trends; specifically, recruits of racial minorities increased their use of e-cigarettes over the past five years faster than Whites. Of concern is what impact this dramatic increase in e-cigarette use will have on overall health and later initiation of combustible tobacco products in the military.

Identification of novel epithelial ovarian cancer loci in women of African ancestry.

Women of African ancestry have lower incidence of epithelial ovarian cancer (EOC) yet worse survival compared to women of European ancestry. We conducted a genome-wide association study in African ancestry women with 755 EOC cases, including 537 high-grade serous ovarian carcinomas (HGSOC) and 1,235 controls. We identified four novel loci with suggestive evidence of association with EOC (p < 1 × 10-6 ), including rs4525119 (intronic to AKR1C3), rs7643459 (intronic to LOC101927394), rs4286604 (12 kb 3' of UGT2A2) and rs142091544 (5 kb 5' of WWC1). For HGSOC, we identified six loci with suggestive evidence of association including rs37792 (132 kb 5' of follistatin [FST]), rs57403204 (81 kb 3' of MAGEC1), rs79079890 (LOC105376360 intronic), rs66459581 (5 kb 5' of PRPSAP1), rs116046250 (GABRG3 intronic) and rs192876988 (32 kb 3' of GK2). Among the identified variants, two are near genes known to regulate hormones and diseases of the ovary (AKR1C3 and FST), and two are linked to cancer (AKR1C3 and MAGEC1). In follow-up studies of the 10 identified variants, the GK2 region SNP, rs192876988, showed an inverse association with EOC in European ancestry women (p = 0.002), increased risk of ER positive breast cancer in African ancestry women (p = 0.027) and decreased expression of GK2 in HGSOC tissue from African ancestry women (p = 0.004). A European ancestry-derived polygenic risk score showed positive associations with EOC and HGSOC in women of African ancestry suggesting shared genetic architecture. Our investigation presents evidence of variants for EOC shared among European and African ancestry women and identifies novel EOC risk loci in women of African ancestry.

Impulsiveness as a predictor of topiramate response for cocaine use disorder.

BACKGROUND/OBJECTIVES: Topiramate has been studied in the treatment of substance use disorders and is often used off-label in the treatment of other disorders with impaired impulse control. We sought to determine whether impulsiveness could predict topiramate treatment response in individuals with cocaine use disorder (CUD). METHODS: In a post-hoc analysis of a 12-week, double-blind, randomized, placebo-controlled trial of topiramate for CUD, we examined the relationship between response to treatment and participants' baseline score on the Barrett Impulsiveness Scale (BIS-11). During the original trial, topiramate was titrated up to 300 mg/day over 6 weeks and maintained for 6 weeks. All participants received weekly cognitive behavioral therapy. RESULTS: Individuals with total BIS-11 scores above the median had 11.2% more cocaine-free days with topiramate versus placebo (Bonferroni corrected p = 0.047). Individuals with first-order factor scores above the median in self-control (Bonferroni corrected p = 0.020) and at or below the median in attention (Bonferroni corrected p = 0.022), and second-order factor scores at or below the median in attentional (Bonferroni corrected p = 0.024) and motor impulsiveness (Bonferroni corrected p = 0.046) were all associated with a greater improvement with topiramate. DISCUSSION/CONCLUSION: The results indicate an association between higher within-group impulsiveness and response to topiramate for CUD. The subscore findings may suggest a complex interaction between effectiveness and known cognitive side effects. The finding that trait impulsiveness is associated with treatment response is a promising discovery that may help guide treatment for CUD. SCIENTIFIC SIGNIFICANCE: This analysis suggests a possible endophenotype based on impulsiveness that can predict treatment response to topiramate. (Am J Addict 2019;XX:1-6).

Genome-wide association study of subclinical interstitial lung disease in MESA.

BACKGROUND: We conducted a genome-wide association study (GWAS) of subclinical interstitial lung disease (ILD), defined as high attenuation areas (HAA) on CT, in the population-based Multi-Ethnic Study of Atherosclerosis Study. METHODS: We measured the percentage of high attenuation areas (HAA) in the lung fields on cardiac CT scan defined as voxels with CT attenuation values between -600 and -250 HU. Genetic analyses were performed in MESA combined across race/ethnic groups: non-Hispanic White (n = 2,434), African American (n = 2,470), Hispanic (n = 2,065) and Chinese (n = 702), as well as stratified by race/ethnicity. RESULTS: Among 7,671 participants, regions at genome-wide significance were identified for basilar peel-core ratio of HAA in FLJ35282 downstream of ANRIL (rs7852363, P = 2.1x10-9) and within introns of SNAI3-AS1 (rs140142658, P = 9.6x10-9) and D21S2088E (rs3079677, P = 2.3x10-8). Within race/ethnic groups, 18 additional loci were identified at genome-wide significance, including genes related to development (FOXP4), cell adhesion (ALCAM) and glycosylation (GNPDA2, GYPC, GFPT1 and FUT10). Among these loci, SNP rs6844387 near GNPDA2 demonstrated nominal evidence of replication in analysis of n = 1,959 participants from the Framingham Heart Study (P = 0.029). FOXP4 region SNP rs2894439 demonstrated evidence of validation in analysis of n = 228 White ILD cases from the Columbia ILD Study compared to race/ethnicity-matched controls from MESA (one-sided P = 0.007). In lung tissue from 15 adults with idiopathic pulmonary fibrosis compared to 15 adults without lung disease. ANRIL (P = 0.001), ALCAM (P = 0.03) and FOXP4 (P = 0.046) were differentially expressed. CONCLUSIONS: Our results suggest novel roles for protein glycosylation and cell cycle disinhibition by long non-coding RNA in the pathogenesis of ILD.

Genetic association of long-chain acyl-CoA synthetase 1 variants with fasting glucose, diabetes, and subclinical atherosclerosis.

Long-chain acyl-CoA synthetase 1 (ACSL1) converts free fatty acids into acyl-CoAs. Mouse studies have revealed that ACSL1 channels acyl-CoAs to ß-oxidation, thereby reducing glucose utilization, and is required for diabetes-accelerated atherosclerosis. The role of ACSL1 in humans is unknown. We therefore examined common variants in the human ACSL1 locus by genetic association studies for fasting glucose, diabetes status, and preclinical atherosclerosis by using the MAGIC and DIAGRAM consortia; followed by analyses in participants from the Multi-Ethnic Study of Atherosclerosis, the Penn-T2D consortium, and a meta-analysis of subclinical atherosclerosis in African Americans; and finally, expression quantitative trait locus analysis and identification of DNase I hypersensitive sites (DHS). The results show that three SNPs in ACSL1 (rs7681334, rs735949, and rs4862423) are associated with fasting glucose or diabetes status in these large (>200,000 subjects) data sets. Furthermore, rs4862423 is associated with subclinical atherosclerosis and coincides with a DHS highly accessible in human heart. SNP rs735949 is in strong linkage disequilibrium with rs745805, significantly associated with ACSL1 levels in skin, suggesting tissue-specific regulatory mechanisms. This study provides evidence in humans of ACSL1 SNPs associated with fasting glucose, diabetes, and subclinical atherosclerosis and suggests links among these traits and acyl-CoA synthesis.

Phenotype of asthmatics with increased airway S-nitrosoglutathione reductase activity.

S-Nitrosoglutathione is an endogenous airway smooth muscle relaxant. Increased airway S-nitrosoglutathione breakdown occurs in some asthma patients. We asked whether patients with increased airway catabolism of this molecule had clinical features that distinguished them from other asthma patients. We measured S-nitrosoglutathione reductase expression and activity in bronchoscopy samples taken from 66 subjects in the Severe Asthma Research Program. We also analysed phenotype and genotype data taken from the program as a whole. Airway S-nitrosoglutathione reductase activity was increased in asthma patients (p=0.032). However, only a subpopulation was affected and this subpopulation was not defined by a "severe asthma" diagnosis. Subjects with increased activity were younger, had higher IgE and an earlier onset of symptoms. Consistent with a link between S-nitrosoglutathione biochemistry and atopy: 1) interleukin 13 increased S-nitrosoglutathione reductase expression and 2) subjects with an S-nitrosoglutathione reductase single nucleotide polymorphism previously associated with asthma had higher IgE than those without this single nucleotide polymorphism. Expression was higher in airway epithelium than in smooth muscle and was increased in regions of the asthmatic lung with decreased airflow. An early-onset, allergic phenotype characterises the asthma population with increased S-nitrosoglutathione reductase activity.

Subgroup Identification in Personalized Treatment of Alcohol Dependence.

BACKGROUND: Identification of patient subgroups to enhance treatment effects is an important topic in personalized (or tailored) alcohol treatment. Recently, several recursive partitioning methods have been proposed to identify subgroups benefiting from treatment. These novel data mining methods help to address the limitations of traditional regression-based methods that focus on interactions. METHODS: We propose an exploratory approach, using recursive partitioning methods, for example, interaction trees (IT) and virtual twins (VT), to flexibly identify subgroups in which the treatment effect is likely to be large. We apply these tree-based methods to a pharmacogenetic trial of ondansetron. RESULTS: Our methods identified several subgroups based on patients' genetic and other prognostic covariates. Among the 251 subjects with complete genotype information, the IT method identified 118 with specific genetic and other prognostic factors, resulting in a 17.2% decrease in the percentage of heavy drinking days (PHDD). The VT method identified 88 subjects with a 21.8% decrease in PHDD. Overall, the VT subgroup achieved a good balance between the treatment effect and the group size. CONCLUSIONS: A data mining approach is proposed as a valid exploratory method to identify a sufficiently large subgroup of subjects that is likely to receive benefit from treatment in an alcohol dependence pharmacotherapy trial. Our results provide new insights into the heterogeneous nature of alcohol dependence and could help clinicians to tailor treatment to the biological profile of individual patients, thereby achieving better treatment outcomes.

Etiology of diarrhea in Bangladeshi infants in the first year of life analyzed using molecular methods.

BACKGROUND: Diarrhea causes enormous morbidity and mortality in developing countries, yet the relative importance of multiple potential enteropathogens has been difficult to ascertain. METHODS: We performed a longitudinal cohort study from birth to 1 year of age in 147 infants in Dhaka, Bangladesh. Using multiplex polymerase chain reaction, we analyzed 420 episodes of diarrhea and 1385 monthly surveillance stool specimens for 32 enteropathogen gene targets. For each infant we examined enteropathogen quantities over time to ascribe each positive target as a probable or less-likely contributor to diarrhea. RESULTS: Multiple enteropathogens were detected by the first month of life. Diarrhea was associated with a state of overall pathogen excess (mean number of enteropathogen gene targets (± SE), 5.6 ± 0.1 vs 4.3 ± 0.1 in surveillance stool specimens; P < .05). After a longitudinal, quantitative approach was applied to filter out less-likely contributors, each diarrheal episode still had an average of 3.3 probable or dominant targets. Enteroaggregative Escherichia coli, Campylobacter, enteropathogenic E. coli, rotavirus, and Entamoeba histolytica were the most frequent probable contributors to diarrhea. Rotavirus was enriched in moderate to severe diarrheal episodes. CONCLUSIONS: In this community-based study diarrhea seemed to be a multipathogen event and a state of enteropathogen excess above a high carriage baseline.

Developing a Text Messaging Intervention to Prevent Binge and Heavy Drinking in a Military Population: Mixed Methods Development Study.

BACKGROUND: Alcohol misuse is the fourth leading cause of death in the United States and a significant problem in the US military. Brief alcohol interventions can reduce negative alcohol outcomes in civilian and military populations, but additional scalable interventions are needed to reduce binge and heavy drinking. SMS text messaging interventions could address this need, but to date, no programs exist for military populations. OBJECTIVE: We aimed to develop an SMS text messaging intervention to address binge and heavy drinking among Airmen in Technical Training in the US Air Force. METHODS: We implemented a 2-phase, mixed methods study to develop the SMS text messaging intervention. In phase 1, a total of 149 respondents provided feedback about the persuasiveness of 49 expert-developed messages, preferences regarding message frequency, timing and days to receive messages, and suggested messages, which were qualitatively coded. In phase 2, a total of 283 respondents provided feedback about the persuasiveness of 77 new messages, including those developed through the refinement of messages from phase 1, which were coded and assessed based on the Behavior Change Technique Taxonomy (BCTT). For both phases, mean persuasiveness scores (range 1-5) were calculated and compared according to age (aged <21 or ≥21 years) and gender. Top-ranking messages from phase 2 were considered for inclusion in the final message library. RESULTS: In phase 1, top-rated message themes were about warnings about adverse outcomes (eg, impaired judgment and financial costs), recommendations to reduce drinking, and invoking values and goals. Through qualitative coding of suggested messages, we identified themes related to warnings about adverse outcomes, recommendations, prioritizing long-term goals, team and belonging, and invoking values and goals. Respondents preferred to receive 1 to 3 messages per week (124/137, 90.5%) and to be sent messages on Friday, Saturday, and Sunday (65/142, 45.8%). In phase 2, mean scores for messages in the final message library ranged from 3.31 (SD 1.29) to 4.21 (SD 0.90). Of the top 5 highest-rated messages, 4 were categorized into 2 behavior change techniques (BCTs): valued self-identity and information about health consequences. The final message library includes 28 BCTT-informed messages across 13 BCTs, with messages having similar scores across genders. More than one-fourth (8/28, 29%) of the final messages were informed by the suggested messages from phase 1. As Airmen aged <21 years face harsher disciplinary action for alcohol consumption, the program is tailored based on the US legal drinking age. CONCLUSIONS: This study involved members from the target population throughout 2 formative stages of intervention development to design a BCTT-informed SMS text messaging intervention to reduce binge and heavy drinking, which is now being tested in an efficacy trial. The results will determine the impact of the intervention on binge drinking and alcohol consumption in the US Air Force.

Venoarterial Extracorporeal Life Support Use in Acute Pulmonary Embolism Shows Favorable Outcomes.

BACKGROUND: Differences in outcomes by indication for venoarterial extracorporeal life support (VA-ECLS) are poorly described. We hypothesized that patients on VA-ECLS for acute pulmonary embolism (PE) have fewer complications and better survival than patients on VA-ECLS for other indications. METHODS: All patients ≥18 years on VA-ECLS from the Extracorporeal Life Support Organization global registry (2010-2019) were evaluated (n = 29,842). After excluding patients aged >79 years (n = 729) and those with incomplete indication data (n = 2530), patients were stratified by VA-ECLS indication for PE vs all other indications. The association between being discharged alive and each type of complication with VA-ECLS indication was assessed. RESULTS: Of 26,583 patients included in the analysis, 978 (3.7%) were on VA-ECLS for a primary diagnosis of acute PE. Acute PE patients were younger (53.1 vs 56.7 years, P < .001) and were more likely to be women (52.1% vs 32.3%, P < .001). Patients who underwent VA-ECLS for acute PE were 78% more likely to be discharged alive vs patients supported with VA-ECLS for other reasons (52.8% vs 40.4%; P < .001). Acute PE patients had fewer cardiovascular and renal complications (26.6% vs 38.0% and 31.1% vs 39.4%, respectively; adjusted P < .001). Acute PE patients had higher odds of having clots and mechanical complications (8.7% vs 7.9% and 16.7% vs 14.6%, respectively; adjusted P < .001). CONCLUSIONS: Patients undergoing VA-ECLS for acute PE have higher odds of survival to hospital discharge compared with those supported for other indications. Additionally, VA-ECLS in this population is associated with fewer cardiovascular and renal complications but higher mechanical complications.

Topiramate's effects on cocaine-induced subjective mood, craving and preference for money over drug taking.

Topiramate, presumably through antagonism of excitatory glutaminergic pathways and facilitation of inhibitory gamma-aminobutyric acid neurons in the cortico-mesolimbic system, might reduce cocaine's abuse liability. We tested whether topiramate (100 mg twice daily) would reduce the euphoria, subjective mood, craving and preference for cocaine over money induced by low and high doses (0.325 and 0.65 mg/kg i.v., respectively) of experimentally administered cocaine in 24 male and female, cocaine-dependent, non-treatment-seeking research volunteers in a university in-patient laboratory. We utilized a randomized, double-blind, placebo-controlled, within-subject, Latin-square cross-over design in which three experimental challenge doses of low-dose cocaine, high-dose cocaine and placebo were administered in counterbalanced order after 5 days of topiramate or matching placebo pre-treatments separated by a 1-week washout period (2006-2009). After placebo pre-treatments, cocaine produced dose-related increases in euphoria, stimulant effects, craving for more cocaine and monetary value of cocaine in a behavioral preference test of cocaine versus money choice. Topiramate pre-treatment reduced the cocaine-related craving and monetary value of high-dose cocaine while increasing the monetary value, euphoria and stimulant effects of low-dose cocaine. Validated and standardized human experimental methods evaluating the potential for topiramate to alter cocaine's abuse liability suggest that topiramate may reduce the reinforcing effects and craving induced by higher cocaine doses. Low-dose cocaine might appear to have some enhancement of its stimulant properties in the presence of topiramate's prominent sedative effects.

Motives for using electronic nicotine delivery systems (ENDS) as a cessation tool are associated with tobacco abstinence at 1-year follow-up: A prospective investigation among young adults in the United States Air Force.

Introduction: Smokers use electronic nicotine delivery systems (ENDS), including e-cigarettes, as a harm reduction strategy even though the Food and Drug Administration (FDA) has not approved them for tobacco cessation. The limited literature about ENDS use for cigarette cessation is concerning for the U.S. military, which is largely comprised of young adults at increased risk for tobacco use. Thus, the current study aims to evaluate use of ENDS products as a cessation tool in relation to point-prevalence tobacco abstinence at one-year follow-up in a cohort of 8,901 U.S. Air Force personnel attending entry-level job training from March 2016 to April 2019. Methods: A propensity-score adjusted multinomial logistic regression model was used to assess the association between the baseline motives for ENDS use (i.e., for cigarette cessation versus alternative reasons) and tobacco use at the one-year follow-up (cigarette use, non-cigarette tobacco product use, and tobacco abstinence) among those reporting history of cigarette use at baseline. Results: Smokers reporting ENDS use for cigarette cessation were more likely to be abstinent at one-year follow-up (Odds Ratio[OR] = 1.62, 95% CI: 1.06-2.49, P =.03) as well as quit using non-cigarette tobacco products (OR = 2.11, 95% CI: 1.65-2.70, P <.001) than those reporting ENDS use for alternative reasons. Conclusions: Current tobacco users are recommended to use FDA-approved products for smoking cessation, such as nicotine replacement therapy. However, given the high prevalence of cigarette use among military populations, ENDS may provide a useful alternative harm reduction strategy for this high-risk population.

Impact of a High-Resolution Anoscopy Clinic on Management of Anal Dysplasia in Women Living With HIV.

BACKGROUND: The rate of anal squamous cell cancer (aSCC) is increasing among women living with HIV. Treatment of precursor high grade squamous intraepithelial lesions (HSIL) may reduce the risk of progression to aSCC. The objective of this study was to examine effects of a dedicated high-resolution anoscopy (HRA) clinic on management of HSIL in women with HIV. METHODS: Women living with HIV who underwent anal dysplasia screening at a single institution between 2006 and 2020 were reviewed. Those who underwent screening before (Group A) and after (Group B) the implementation of an HRA program in 2017 were compared. The primary outcome of interest was the successful detection and treatment of HSIL. RESULTS: A total of 201 women living with HIV underwent anal dysplasia screening between 2006 and 2020. Seventy-seven patients were found to have abnormal anal cytology requiring further treatment: 43 (55.8%) in Group A and 34 (44.2%) patients in Group B. Of the patients with abnormal anal cytology, 76.7% of patients in Group A received further biopsy and treatment, whereas 79.4% of Group B patients underwent subsequent biopsy and treatment. In propensity score weighting logistic regression analysis, the Group B was 4.6 times as likely to diagnosis HSIL on biopsy compared to Group A (OR = 4.60, 95% CI: 1.15 to 18.38, P = .03). CONCLUSIONS: Anal dysplasia is common among women living with HIV. The establishment of a HRA program was associated with increased identification and treatment of HSIL among women living with HIV, which may prevent the progression to aSCC.

Predictors of Re-Engagement after Relapse in a Tobacco Quit Line Intervention: Secondary Analysis from a Randomized Clinical Trial.

People who smoke often make several quit attempts before successfully maintaining abstinence. Therefore, incorporating re-engagement for people who fail to initially quit could increase quit attempts and ultimately increase cessation rates. Within the context of quit line-based interventions, it remains unknown what characteristics are associated with re-engagement. The purpose of this study was to assess associations between demographic and motivational characteristics, tobacco use, and initial intervention engagement with re-engagement in a tobacco quit line intervention. Among 372 adults who reported smoking three months after initiating a quit line-facilitated quit attempt as part of a larger randomized clinical trial, associations between personal characteristics (e.g., age, gender, nicotine dependence, and confidence in their ability to quit smoking) and initial intervention engagement (number of completed counseling sessions and use of nicotine replacement therapy (NRT)) with re-engagement (accepting an offer to re-initiate the quit line intervention) were determined using multivariable logistic regression modeling. Compared to non-White participants, White participants had lower odds of re-engaging (OR: 0.42, 95% CI: 0.23, 0.75). Number of initial counseling sessions completed was associated with re-engaging. NRT use during the initial intervention was not associated with re-engaging. Initial intervention engagement is important in the process of re-engagement, specifically attending counseling sessions. Exploration of associations between initial intervention engagement and potentially modifiable motivational factors is needed to be potentially leveraged in future interventions to maintain continued engagement in cessation among adults who smoke.

Alanyl-glutamine supplementation for Clostridioides difficile infection treatment (ACT): a double-blind randomised controlled trial study protocol.

INTRODUCTION: Clostridioides difficile is the leading cause of healthcare-associated infections in the USA, with an estimated 1 billion dollars in excess cost to the healthcare system annually. C. difficile infection (CDI) has high recurrence rate, up to 25% after first episode and up to 60% for succeeding episodes. Preliminary in vitro and in vivo studies indicate that alanyl-glutamine (AQ) may be beneficial in treating CDI by its effect on restoring intestinal integrity in the epithelial barrier, ameliorating inflammation and decreasing relapse. METHODS AND ANALYSIS: This study is a randomised, placebo-controlled, double-blind, phase II clinical trial. The trial is designed to determine optimal dose and safety of oral AQ at 4, 24 and 44 g doses administered daily for 10 days concurrent with standard treatment of non-severe or severe uncomplicated CDI in persons age 18 and older. The primary outcome of interest is CDI recurrence during 60 days post-treatment follow-up, with the secondary outcome of mortality during 60 days post-treatment follow-up. Exploratory analysis will be done to determine the impact of AQ supplementation on intestinal and systemic inflammation, as well as intestinal microbial and metabolic profiles. ETHICS AND DISSEMINATION: The study has received University of Virginia Institutional Review Board approval (HSR200046, Protocol v9, April 2023). Findings will be disseminated via conference presentations, lectures and peer-reviewed publications. TRIAL REGISTRATION NUMBER: NCT04305769.