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Alcohol consumption level and alcohol use disorder (AUD) diagnosis are moderately heritable traits. We conduct genome-wide association studies of these traits using longitudinal Alcohol Use Disorder Identification Test-Consumption (AUDIT-C) scores and AUD diagnoses in a multi-ancestry Million Veteran Program sample ( N  = 274,424). We identify 18 genome-wide significant loci: 5 associated with both traits, 8 associated with AUDIT-C only, and 5 associated with AUD diagnosis only. Polygenic Risk Scores (PRS) for both traits are associated with alcohol-related disorders in two independent samples. Although a significant genetic correlation reflects the overlap between the traits, genetic correlations for 188 non-alcohol-related traits differ significantly for the two traits, as do the phenotypes associated with the traits’ PRS. Cell type group partitioning heritability enrichment analyses also differentiate the two traits. We conclude that, although heavy drinking is a key risk factor for AUD, it is not a sufficient cause of the disorder. The genetic underpinnings of alcohol use disorder and consumption are incompletely understood. Here, the authors perform GWAS for Alcohol Use Disorder (AUD) Identification Test-Consumption scores and AUD diagnosis from electronic health records of 274,424 individuals and identify a total of 18 associated loci.

In the absence of official clinical trial information, data from social networks can be used by public health and medical researchers to assess public claims about loosely regulated substances such as cannabidiol (CBD). For example, this can be achieved by comparing the medical conditions targeted by those selling CBD against the medical conditions patients commonly treat with CBD. The objective of this study was to provide a framework for public health and medical researchers to use for identifying and analyzing the consumption and marketing of unregulated substances. Specifically, we examined CBD, which is a substance that is often presented to the public as medication despite complete evidence of efficacy and safety. We collected 567,850 tweets by searching Twitter with the Tweepy Python package using the terms \"CBD\" and \"cannabidiol.\" We trained two binary text classifiers to create two corpora of 167,755 personal use and 143,322 commercial/sales tweets. Using medical, standard, and slang dictionaries, we identified and compared the most frequently occurring medical conditions, symptoms, side effects, body parts, and other substances referenced in both corpora. In addition, to assess popular claims about the efficacy of CBD as a medical treatment circulating on Twitter, we performed sentiment analysis via the VADER (Valence Aware Dictionary for Sentiment Reasoning) model on the personal CBD tweets. We found references to medically relevant terms that were unique to either personal or commercial CBD tweet classes, as well as medically relevant terms that were common to both classes. When we calculated the average sentiment scores for both personal and commercial CBD tweets referencing at least one of 17 medical conditions/symptoms terms, an overall positive sentiment was observed in both personal and commercial CBD tweets. We observed instances of negative sentiment conveyed in personal CBD tweets referencing autism, whereas CBD was also marketed multiple times as a treatment for autism within commercial tweets. Our proposed framework provides a tool for public health and medical researchers to analyze the consumption and marketing of unregulated substances on social networks. Our analysis showed that most users of CBD are satisfied with it in regard to the condition that it is being advertised for, with the exception of autism.

Background The aim of this study was to determine the 3-month efficacy of a single-session, clinic-based intervention promoting condom use for anal and oral sex among HIV-uninfected Black young men who have sex with men (YBMSM). A pre-post test randomised controlled trial (RCT) was conducted from 2012 to 2015 using a 3-month period of observation. Recruitment and assessment occurred in sexually transmissible infection (STI) clinics. Men were randomised to either the intervention condition (n=142) or a standard-of-care control condition (n=135). The experimental condition comprised a single session of a one-to-one program designed for use in STI clinics. YBMSM completed both baseline and 3-month follow-up assessments. Outcomes measures were condomless anal insertive sex, condomless anal receptive sex and condomless oral sex. Among men receiving the intervention, 11.2% (n=15) reported any condomless anal insertive sex at follow-up, compared with 20.6% (n=27) among controls (rate ratio=0.54, P=0.04). In addition, 12.0% (n=17) of men receiving the intervention reported any condomless anal receptive sex at follow-up, compared with 21.6% (n=29) among controls (rate ratio=0.55, P=0.03). When combining insertive and receptive anal sex, 18.3% (n=26) of men receiving the intervention reported any condomless sex, compared with 31.1% (n=42) among controls (rate ratio=0.59, P=0.01). Furthermore, 45.8% (n=33) of men receiving the intervention reported any condomless oral sex at follow-up, compared with 63.2% (n=48) among controls (rate ratio=0.72, P=0.03). This analysis of data from a Phase 3 RCT suggests that a single session of a clinic-based behavioural intervention may effectively promote the consistent use of condoms for anal and oral sex among HIV-uninfected YBMSM. The single-session program may be a valuable counselling tool for use in conjunction with recommended quarterly clinic appointments for YBMSM using pre-exposure prophylaxis.

Here we report a large genome-wide association study (GWAS) for longitudinal smoking phenotypes in 286,118 individuals from the Million Veteran Program (MVP) where we identified 18 loci for smoking trajectory of current versus never in European Americans, one locus in African Americans, and one in Hispanic Americans. Functional annotations prioritized several dozen genes where significant loci co-localized with either expression quantitative trait loci or chromatin interactions. The smoking trajectories were genetically correlated with 209 complex traits, for 33 of which smoking was either a causal or a consequential factor. We also performed European-ancestry meta-analyses for smoking status in the MVP and GWAS & Sequencing Consortium of Alcohol and Nicotine use (GSCAN) (N total  = 842,717) and identified 99 loci for smoking initiation and 13 loci for smoking cessation. Overall, this large GWAS of longitudinal smoking phenotype in multiple populations, combined with a meta-GWAS for smoking status, adds new insights into the genetic vulnerability for smoking behavior. Genome-wide association studies (GWASs) for cigarette smoking have identified several hundred loci that account for a small proportion of the overall genetic risk. Here, the authors report a large GWAS for smoking trajectories and meta-analysis for smoking status, finding multiple plausible loci.

Recent media reports commented about a possible issue of the misuse of antidiabetics related to molecules promoted as a weight-loss treatment in non-obese people. We evaluated here available pharmacovigilance misuse/abuse signals related to semaglutide, a glucagon-like peptide-1 (GLP-1) analogue, in comparison to other GLP-1 receptor agonists (albiglutide, dulaglutide, exenatide, liraglutide, lixisenatide, and tirzepatide) and the phentermine–topiramate combination. To acheieve that aim, we analyzed the Food and Drug Administration’s FDA Adverse Events Reporting System (FAERS) dataset, performing a descriptive analysis of adverse event reports (AERs) and calculating related pharmacovigilance measures, including the reporting odds ratio (ROR) and the proportional reporting ratio (PRR). During January 2018–December 2022, a total of 31,542 AERs involving the selected molecules were submitted to FAERS; most involved dulaglutide (n = 11,858; 37.6%) and semaglutide (n = 8249; 26.1%). In comparing semaglutide vs. the remaining molecules, the respective PRR values of the AERs ‘drug abuse’, ‘drug withdrawal syndrome’, ‘prescription drug used without a prescription’, and ‘intentional product use issue’ were 4.05, 4.05, 3.60, and 1.80 (all < 0.01). The same comparisons of semaglutide vs. the phentermine–topiramate combination were not associated with any significant differences. To the best of our knowledge, this is the first study documenting the misuse/abuse potential of semaglutide in comparison with other GLP1 analogues and the phentermine–topiramate combination. The current findings will need to be confirmed by further empirical investigations to fully understand the safety profile of those molecules.

Despite increasing reports, antidepressant (AD) misuse and dependence remain underestimated issues, possibly due to limited epidemiological and pharmacovigilance evidence. Thus, here we aimed to determine available pharmacovigilance misuse/abuse/dependence/withdrawal signals relating to the Selective Serotonin Reuptake Inhibitors (SSRI) citalopram, escitalopram, paroxetine, fluoxetine, and sertraline. Both EudraVigilance (EV) and Food and Drug Administration-FDA Adverse Events Reporting System (FAERS) datasets were analysed to identify AD misuse/abuse/dependence/withdrawal issues. A descriptive analysis was performed; moreover, pharmacovigilance measures, including the reporting odds ratio (ROR), the proportional reporting ratio (PRR), the information component (IC), and the empirical Bayesian geometric mean (EBGM) were calculated. Both datasets showed increasing trends of yearly reporting and similar signals regarding abuse and dependence. From the EV, a total of 5335 individual ADR reports were analysed, of which 30% corresponded to paroxetine (n = 1592), 27% citalopram (n = 1419), 22% sertraline (n = 1149), 14% fluoxetine (n = 771), and 8% escitalopram (n = 404). From FAERS, a total of 144,395 individual ADR reports were analysed, of which 27% were related to paroxetine, 27% sertraline, 18% citalopram, 16% fluoxetine, and 13% escitalopram. Comparing SSRIs, the EV misuse/abuse-related ADRs were mostly recorded for citalopram, fluoxetine, and sertraline; conversely, dependence was mostly associated with paroxetine, and withdrawal to escitalopram. Similarly, in the FAERS dataset, dependence/withdrawal-related signals were more frequently reported for paroxetine. Although SSRIs are considered non-addictive pharmacological agents, a range of proper withdrawal symptoms can occur well after discontinuation, especially with paroxetine. Prescribers should be aware of the potential for dependence and withdrawal associated with SSRIs.

In the past twenty years, the consumption of opioid medications has reached significant proportions, leading to a rise in drug misuse and abuse and increased opioid dependence and related fatalities. Thus, the purpose of this study was to determine whether there are pharmacovigilance signals of abuse, misuse, and dependence and their nature for the following prescription opioids: codeine, dihydrocodeine, fentanyl, oxycodone, pentazocine, and tramadol. Both the pharmacovigilance datasets EudraVigilance (EV) and the FDA Adverse Events Reporting System (FAERS) were analyzed to identify and describe possible misuse-/abuse-/dependence-related issues. A descriptive analysis of the selected Adverse Drug Reactions (ADRs) was performed, and pharmacovigilance signal measures (i.e., reporting odds ratio, proportional reporting ratio, information component, and empirical Bayesian geometric mean) were computed for preferred terms (PTs) of abuse, misuse, dependence, and withdrawal, as well as PTs eventually related to them (e.g., aggression). From 2003 to 2018, there was an increase in ADR reports for the selected opioids in both datasets. Overall, 16,506 and 130,293 individual ADRs for the selected opioids were submitted to EV and FAERS, respectively. Compared with other opioids, abuse concerns were mostly recorded in relation to fentanyl and oxycodone, while tramadol and oxycodone were more strongly associated with drug dependence and withdrawal. Benzodiazepines, antidepressants, other opioids, antihistamines, recreational drugs (e.g., cocaine and alcohol), and several new psychoactive substances, including mitragynine and cathinones, were the most commonly reported concomitant drugs. ADRs reports in pharmacovigilance databases confirmed the availability of data on the abuse and dependence of prescription opioids and should be considered a resource for monitoring and preventing such issues. Psychiatrists and clinicians prescribing opioids should be aware of their misuse and dependence liability and effects that may accompany their use, especially together with concomitant drugs.

Given ongoing challenges in non-invasive non-alcoholic liver disease (NAFLD) diagnosis, we sought to validate an ALT-based NAFLD phenotype using measures readily available in electronic health records (EHRs) and population-based studies by leveraging the clinical and genetic data in the Million Veteran Program (MVP), a multi-ethnic mega-biobank of US Veterans. MVP participants with alanine aminotransferases (ALT) >40 units/L for men and >30 units/L for women without other causes of liver disease were compared to controls with normal ALT. Genetic variants spanning eight NAFLD risk or ALT-associated loci (LYPLAL1, GCKR, HSD17B13, TRIB1, PPP1R3B, ERLIN1, TM6SF2, PNPLA3) were tested for NAFLD associations with sensitivity analyses adjusting for metabolic risk factors and alcohol consumption. A manual EHR review assessed performance characteristics of the NAFLD phenotype with imaging and biopsy data as gold standards. Genetic associations with advanced fibrosis were explored using FIB4, NAFLD Fibrosis Score and platelet counts. Among 322,259 MVP participants, 19% met non-invasive criteria for NAFLD. Trans-ethnic meta-analysis replicated associations with previously reported genetic variants in all but LYPLAL1 and GCKR loci (P<6x10-3), without attenuation when adjusted for metabolic risk factors and alcohol consumption. At the previously reported LYPLAL1 locus, the established genetic variant did not appear to be associated with NAFLD, however the regional association plot showed a significant association with NAFLD 279kb downstream. In the EHR validation, the ALT-based NAFLD phenotype yielded a positive predictive value 0.89 and 0.84 for liver biopsy and abdominal imaging, respectively (inter-rater reliability (Cohen's kappa = 0.98)). HSD17B13 and PNPLA3 loci were associated with advanced fibrosis. We validate a simple, non-invasive ALT-based NAFLD phenotype using EHR data by leveraging previously established NAFLD risk-associated genetic polymorphisms.

To test the efficacy of a single-session, clinic-based intervention designed to promote condom use among young black men who have sex with men (YBMSM). Six hundred YBMSM were enrolled in a randomized controlled trial, using a 12-month observation period. An intent-to-treat analysis was performed, with multiple imputation for missing data. Compared with the reference group, human immunodeficiency virus (HIV)-infected men in the intervention group had 64% greater odds of reporting consistent condom use for anal receptive sex over 12 months (estimated odds ratio, 1.64; 95% confidence interval, 1.23-2.17, P = 0.001). Also, compared with the reference group, HIV-uninfected men in the intervention group had more than twice the odds of reporting consistent condom use for anal receptive sex over 12 months (estimated odds ratio, 2.14; 95% confidence interval, 1.74-2.63, P < 0.001). Significant intervention effects relative to incident sexually transmitted diseases were not observed. A single-session, clinic-based, intervention may help protect HIV-uninfected YBMSM against HIV acquisition and HIV-infected YBMSM from transmitting the virus to insertive partners.

Background The Stay Safe Study is the first observational prospective cohort study investigating fentanyl test strip (FTS) use by people who use drugs (PWUD) and distribution by community organizations that provide harm reduction services (e.g., naloxone distribution) in three states (Kentucky, New York, and Ohio). The purpose of this paper is to describe the study design, along with implementation successes and challenges. A related goal is to provide recommendations and encourage researchers to undertake multi-state and multilevel studies of FTS use and distribution. Methods The Stay Safe Study has one primary, five secondary, and three exploratory objectives. From May-December 2023, we collected survey, interview, and oral fluid drug test data with the primary population of PWUD attending service locations of partner organizations that distribute FTS. We collected survey and interview data with a population of community organizations providing harm reduction services that have a distribution relationship to FTS. There was no intervention, and the study did not distribute FTS. Results A total of 1,156 PWUD participants were enrolled in the study and were invited to complete four weekly survey assessments. Of these, 732 PWUD participants (97.6% of the target) completed at least two of the four weekly surveys and reported drug use at least once during the 28-day observation period. A subset of enrolled participants completed a one-time oral fluid data collection visit (48-hour self-report survey and oral fluid specimen collection) ( n  = 267) and one-on-one semi-structured interviews ( n  = 120). From the population of 36 organizations providing harm reduction services, employees of 28 (78%) in 22 counties across 3 states completed a web-based survey and employees of 24 (66.7%) completed an interview. Study findings will be presented in subsequent publications [ 1 , 2 ]. Conclusion The research team successfully enrolled a large sample of PWUD participants and organizations that provide harm reduction services in three states, followed a cohort of PWUD participants, and generated rich data using three types of instruments. Factors contributing to implementation success include drawing on the community expertise of the parent HEALing Communities Study, selecting incentive amounts that acknowledged the time and expertise of PWUD participants, centralizing survey data collection, and tracking implementation challenges and solutions. Areas of implementation complexity included conducting research on site at the service locations of 14 partner organizations, facilitating timely incentive payments, overseeing research staff, and returning oral fluid results to PWUD participants.