GLP-1 Receptor Agonists and Related Mental Health Issues; Insights from a Range of Social Media Platforms Using a Mixed-Methods Approach

© 2023 by the authors. Licensee MDPI, Basel, Switzerland. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY), https://creativecommons.org/licenses/by/4.0/The emergence of glucagon-like peptide-1 receptor agonists (GLP-1 RAs; semaglutide and others) now promises effective, non-invasive treatment of obesity for individuals with and without diabetes. Social media platforms’ users started promoting semaglutide/Ozempic as a weight-loss treatment, and the associated increase in demand has contributed to an ongoing worldwide shortage of the drug associated with levels of non-prescribed semaglutide intake. Furthermore, recent reports emphasized some GLP-1 RA-associated risks of triggering depression and suicidal thoughts. Consistent with the above, we aimed to assess the possible impact of GLP-1 RAs on mental health as being perceived and discussed in popular open platforms with the help of a mixed-methods approach. Reddit posts yielded 12,136 comments, YouTube videos 14,515, and TikTok videos 17,059, respectively. Out of these posts/entries, most represented matches related to sleep-related issues, including insomnia (n = 620 matches); anxiety (n = 353); depression (n = 204); and mental health issues in general (n = 165). After the initiation of GLP-1 RAs, losing weight was associated with either a marked improvement or, in some cases, a deterioration, in mood; increase/decrease in anxiety/insomnia; and better control of a range of addictive behaviors. The challenges of accessing these medications were a hot topic as well. To the best of our knowledge, this is the first study documenting if and how GLP-1 RAs are perceived as affecting mood, mental health, and behaviors. Establishing a clear cause-and-effect link between metabolic diseases, depression and medications is difficult because of their possible reciprocal relationship, shared underlying mechanisms and individual differences. Further research is needed to better understand the safety profile of these molecules and their putative impact on behavioral and non-behavioral addictions.Peer reviewe

Benzodiazepine Boom: Tracking Etizolam, Pyrazolam, and Flubromazepam from Pre-UK Psychoactive Act 2016 to Present Using Analytical and Social Listening Techniques

© 2024 The Author(s). Licensee MDPI, Basel, Switzerland. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY), https://creativecommons.org/licenses/by/4.0/Introduction: The designer benzodiazepine (DBZD) market continues to expand whilst evading regulatory controls. The widespread adoption of social media by pro-drug use communities encourages positive discussions around DBZD use/misuse, driving demand. This research addresses the evolution of three popular DBZDs, etizolam (E), flubromazepam (F), and pyrazolam (P), available on the drug market for over a decade, comparing the quantitative chemical analyses of tablet samples, purchased from the internet prior to the implementation of the Psychoactive Substances Act UK 2016, with the thematic netnographic analyses of social media content. Method: Drug samples were purchased from the internet in early 2016. The characterisation of all drug batches were performed using UHPLC-MS and supported with 1H NMR. In addition, netnographic studies across the platforms X (formerly Twitter) and Reddit, between 2016–2023, were conducted. The latter was supported by both manual and artificial intelligence (AI)-driven thematic analyses, using numerous.ai and ChatGPT, of social media threads and discussions. Results: UHPLC-MS confirmed the expected drug in every sample, showing remarkable inter/intra batch variability across all batches (E = 13.8 ± 0.6 to 24.7 ± 0.9 mg; F = 4.0 ± 0.2 to 23.5 ± 0.8 mg; P = 5.2 ± 0.2 to 11.5 ± 0.4 mg). 1H NMR could not confirm etizolam as a lone compound in any etizolam batch. Thematic analyses showed etizolam dominated social media discussions (59% of all posts), with 24.2% of posts involving sale/purchase and 17.8% detailing new administration trends/poly-drug use scenarios. Artificial intelligence confirmed three of the top five trends identified manually. Conclusions: Purity variability identified across all tested samples emphasises the increased potential health risks associated with DBZD consumption. We propose the global DBZD market is exacerbated by surface web social media discussions, recorded across X and Reddit. Despite the appearance of newer analogues, these three DBZDs remain prevalent and popularised. Reporting themes on harm/effects and new developments in poly-drug use trends, demand for DBZDs continues to grow, despite their potent nature and potential risk to life. It is proposed that greater controls and constant live monitoring of social media user content is warranted to drive active regulation strategies and targeted, effective, harm reduction strategies.Peer reviewe

Is There a Risk for Semaglutide Misuse? Focus on the Food and Drug Administration’s FDA Adverse Events Reporting System (FAERS) Pharmacovigilance Dataset

© 2023 The authors. Licensee MDPI, Basel, Switzerland. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY), https://creativecommons.org/licenses/by/4.0/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.Peer reviewe

Oxidative Leaching Kinetics of Vanadium from Egyptian Boiler Ash under Acidic Oxidizing Conditions

Processing of Egyptian boiler ash in sulphuric acid solution using hydrogen peroxide as oxidant has been investigated. The results showed that leaching temperature, hydrogen peroxide, sulphuric acid concentration, leaching time, liquid-to-solid ratio and agitation speed, have significant effect; optimum process operating parameters were established as follows: temperature: 9

Modeling the time varying volatility of housing returns: Further evidence from the U.S. Metropolitan condominium markets

This study extends the literature on modeling the volatility of housing returns to the case of condominium returns for five major U.S. metropolitan areas (Boston, Chicago, Los Angeles, New York, and San Francisco). Through the estimation of ARMA models for the respective condominium returns, we find volatility clustering of the residuals. The results from an ARMA-TGARCH-M model reveal the absence of asymmetry in the conditional variance. Dummy variables associated with the housing market collapse unique to each metropolitan area were statistically insignificant in the conditional variance equation, but negative and statistically significant in the mean equation. Condominium markets in Los Angeles and San Francisco exhibit the greatest persistence to volatility shocks.N/

Differential Analysis of Ovarian and Endometrial Cancers Identifies a Methylator Phenotype

Despite improved outcomes in the past 30 years, less than half of all women diagnosed with epithelial ovarian cancer live five years beyond their diagnosis. Although typically treated as a single disease, epithelial ovarian cancer includes several distinct histological subtypes, such as papillary serous and endometrioid carcinomas. To address whether the morphological differences seen in these carcinomas represent distinct characteristics at the molecular level we analyzed DNA methylation patterns in 11 papillary serous tumors, 9 endometrioid ovarian tumors, 4 normal fallopian tube samples and 6 normal endometrial tissues, plus 8 normal fallopian tube and 4 serous samples from TCGA. For comparison within the endometrioid subtype we added 6 primary uterine endometrioid tumors and 5 endometrioid metastases from uterus to ovary. Data was obtained from 27,578 CpG dinucleotides occurring in or near promoter regions of 14,495 genes. We identified 36 locations with significant increases or decreases in methylation in comparisons of serous tumors and normal fallopian tube samples. Moreover, unsupervised clustering techniques applied to all samples showed three major profiles comprising mostly normal samples, serous tumors, and endometrioid tumors including ovarian, uterine and metastatic origins. The clustering analysis identified 60 differentially methylated sites between the serous group and the normal group. An unrelated set of 25 serous tumors validated the reproducibility of the methylation patterns. In contrast, >1,000 genes were differentially methylated between endometrioid tumors and normal samples. This finding is consistent with a generalized regulatory disruption caused by a methylator phenotype. Through DNA methylation analyses we have identified genes with known roles in ovarian carcinoma etiology, whereas pathway analyses provided biological insight to the role of novel genes. Our finding of differences between serous and endometrioid ovarian tumors indicates that intervention strategies could be developed to specifically address subtypes of epithelial ovarian cancer

Primary 3-Month Outcomes of a Double-Blind Randomized Prospective Study (The QUEST Study) Assessing Effectiveness and Safety of Novel High-Frequency Electric Nerve Block System for Treatment of Post-Amputation Pain

Leonardo Kapural,1 Jim Melton,2 Billy Kim,3 Priyesh Mehta,4 Abindra Sigdel,5 Alexander Bautista,6 Erika A Petersen,7 Konstantin V Slavin,8,9 John Eidt,10 Jiang Wu,11 Said Elshihabi,12 Jason Matthew Schwalb,13 H Edward Garrett Jr,14 Elias Veizi,15 Giancarlo Barolat,16 Ravi R Rajani,17 Peter C Rhee,18 Maged Guirguis,19 Nagy Mekhail20 1Carolinas Pain Institute and Center for Clinical Research, Winston-Salem, NC, USA; 2Department of Vascular Surgery, Cardiovascular Health Clinic, Oklahoma City, OK, USA; 3Department of Vascular Surgery, The Surgical Clinic, Nashville, TN, USA; 4Department of Pain Medicine, Meta Medical Research Institute, Dayton, OH, USA; 5Department of Surgery, University of Louisville, Louisville, KY, USA; 6Department of Anesthesiology and Perioperative Medicine, University of Louisville, Louisville, KY, USA; 7Department of Neurosurgery, University of Arkansas, Little Rock, AR, USA; 8Department of Neurosurgery, University of Illinois at Chicago, Chicago, IL, USA; 9Department of Neurology, Jesse Brown VA Medical Center, Chicago, IL, USA; 10Department of Vascular Surgery, Baylor Scott and White Heart and Vascular Hospital Dallas, Dallas, TX, USA; 11Department of Anesthesiology & Pain Medicine, University of Washington Medical Center, Seattle, WA, USA; 12Department of Neurosurgery, Legacy Brain & Spine Surgical Center, Atlanta, GA, USA; 13Department of Neurosurgery, Henry Ford Medical Group, Detroit, MI, USA; 14Department of Vascular Surgery, University of Tennessee-Memphis, Memphis, TN, USA; 15Department of Pain Medicine, VA Northeast OH Healthcare System, Cleveland, OH, USA; 16Department of Neurosurgery, Barolat Neuroscience, Presbyterian/St Luke’s Medical Center, Denver, CO, USA; 17Department of Vascular Surgery, Emory University and Grady Memorial Hospital, Atlanta, GA, USA; 18Department of Orthopedic Surgery, Mayo Clinic, Rochester, MN, USA; 19Department of Interventional Pain Management, Ochsner Health System, New Orleans, LA, USA; 20Department of Pain Management, Cleveland Clinic, Cleveland, OH, USACorrespondence: Leonardo Kapural, Carolinas Pain Institute and Center for Clinical Research, 145 Kimel Park Dr &num;330, Winston-Salem, NC, 27103, USA, Email [email protected]: This multicenter, randomized, double-blinded, active sham-controlled pivotal study was designed to assess the efficacy and safety of high-frequency nerve block treatment for chronic post-amputation and phantom limb pain.Patients and Methods: QUEST enrolled 180 unilateral lower-limb amputees with severe post-amputation pain, 170 of whom were implanted with the Altius device, were randomized 1:1 to active-sham or treatment groups and reached the primary endpoint. Responders were those subjects who received ≥ 50% pain relief 30 min after treatment in ≥ 50% of their self-initiated treatment sessions within the 3-month randomized period. Differences between the active treatment and sham control groups as well as numerous secondary outcomes were determined.Results: At 30-min, (primary outcome), 24.7% of the treatment group were responders compared to 7.1% of the control group (p=0.002). At 120-minutes following treatment, responder rates were 46.8% in the Treatment group and 22.2% in the Control group (p=0.001). Improvement in Brief Pain Inventory interference score of 2.3 ± 0.29 was significantly greater in treatment group than the 1.3 ± 0.26-point change in the Control group (p = 0.01). Opioid usage, although not significantly different, trended towards a greater reduction in the treatment group than in the control group. The incidence of adverse events did not differ significantly between the treatment and control groups.Conclusion: The primary outcomes of the study were met, and the majority of Treatment patients experienced a substantial improvement in PAP (regardless of meeting the study definition of a responder). The significant in PAP was associated with significantly improved QOL metrics, and a trend towards reduced opioid utilization compared to Control. These data indicate that Altius treatment represents a significant therapeutic advancement for lower-limb amputees suffering from chronic PAP.Keywords: post-amputation pain, phantom limb pain, neuromodulation, peripheral nerve stimulation, high-frequency nerve bloc