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Objective: A high plasma cholesterol level is a major predisposing factor for coronary artery disease, and new treatments are currently under consideration. Supported by the close relationship between cholesterol and bile acid metabolism, recent studies have reported a hypocholesterolaemic effect of the bile acid ursodeoxycholic acid (UDCA) in patients with primary biliary cirrhosis but, unfortunately, no data are available in primary hypercholesterolaemia. We performed this study to evaluate the effects of oral administration of UDCA on serum lipoprotein patterns in patients with primary hypercholesterolaemia. Design and Setting: A double-blind, placebo-controlled, crossover study with a 4-week washout period carried out at an outpatient clinic at a university hospital. Study Participants: Twelve individuals with a total serum cholesterol level >5.17 mmol/L. Intervention: Patients were assigned to receive UDCA (8 to 10 mg/kg/day) or placebo for 28 days. They then crossed over to receive the other treatment after a 4-week washout period. Main Outcome Measures and Results: Serum total, low density lipoprotein (LDL), high density lipoprotein (HDL), very low density lipoprotein (VLDL) cholesterol and apoprotein A and B were determined before and after 28-day UDCA and placebo administration. After UDCA administration, the mean (±SD) total serum cholesterol level decreased significantly from 6.37 ± 1.01 mmol/L to 6.06 ± 0.97 mmmol/L (F = 5.7, p = 0.041); no significant differences from baseline were observed in LDL, HDL, VLDL cholesterol, apoprotein A and B. No significant changes in serum lipid parameters occurred after the placebo period. When compared with placebo, the UDCA-induced decrease in total serum cholesterol levels was statistically significant (F = 5.5, p = 0.043). Conclusion: This study shows that UDCA reduces total serum cholesterol levels in patients with mild to moderate hypercholesterolaemia. This effect suggests that the administration of UDCA may improve cholesterol metabolism in these individuals. [ABSTRACT FROM AUTHOR]

Context: The illicit drug landscape in the United States is dynamic, featuring a risky and erratic drug supply. Drug checking programs (DCP) have been successfully implemented and studied extensively in Canada and Europe but are scarce in the United States. Integrating DCP at harm reduction programs provides an opportunity to engage people at the point-of-care and deliver a combination of harm reduction services, access to healthcare services, and linkages to treatment., Program: The New York State Department of Health (NYSDOH) developed and supports operation of 8 pilot community DCP sites throughout the state. The DCP were trained to utilize Fourier-transform infrared spectroscopy (FTIR) technology to deliver real-time results to participants., Implementation: The NYSDOH community DCP pilot began development in 2022. Partnerships were formed across multiple domains including other DCP, universities, forensic laboratories, syringe service and harm reduction programs, and legal and regulatory offices within the NYSDOH. The first pilot sites began operating in mid-2023 and program expansion is on-going., Evaluation: Evaluation staff were extensively engaged in development and implementation phases. Qualitative evaluation focused on barriers, facilitators, and lessons learned from program staff and technicians. Quantitative evidence was gathered to assess the reach of the DCP and accuracy of results attained by drug checking technicians during their training periods. Drug checking results helped characterize the illicit drug supply., Discussion: Development and implementation of DCP in NYS was facilitated by strong partnerships across sectors including public health and harm reduction. DCP may involve diverse partners who do not regularly collaborate, and health departments are positioned to build relationships and convene partners for program implementation. Evaluation findings highlight the importance of facilitating on-going training and technical assistance to DCP for quality assurance. The initial successes and lessons learned from the NYSDOH DCP demonstrate state public health departments' ability to successfully deploy this innovative harm reduction strategy., Competing Interests: The authors have indicated they have no potential conflicts of interest to disclose., (Copyright © 2024 The Authors. Published by Wolters Kluwer Health, Inc.)

Background: Cytisine is an alkaloid that is molecularly similar to nicotine and it is commonly used to treat smoking cessation. While it is considered a reasonably safe treatment option, cytisine intoxication in humans exhibits several adverse effects. These involve the gastrointestinal system (nausea, vomiting, diarrhea), the central nervous system (drowsiness, fatigue, delirium), and the motor system (muscle twitching and fasciculation, difficulties in walking)., Case Presentation: We present a unique case report in which a Caucasian patient (an Italian 64-year-old woman) who was undergoing smoking cessation treatment with cytisine, and due to her misunderstanding of the therapeutic indications provided, took twice the recommended dose every day for 8 days, leading to an intake of 54 mg/dl of cytisine for 3 consecutive days. Notwithstanding the high dosage, the patient did not report any adverse reactions., Conclusion: This confirms the safety of the drug, even at high doses, in patients aiming to quit smoking., Competing Interests: Declarations. Ethics approval and consent to participate: This study was approved by the Ethical Review Board of the University Hospital (approval code 683CESC). Consent for publication: Written informed consent was obtained from the patient for publication of this case report and any accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal. Competing interests: None., (© 2024. The Author(s).)

Benzodiazepine (BDZ) addiction is a widespread and multifaceted phenomenon. For many patients, especially females, the concomitant use of other drugs also increases their risk of QTc prolongation, possibly leading to complications such as seizures and even sudden death. However, the relationship between BDZ use and QTc prolongation is currently unclear. The present study aims to examine patterns of polysubstance use among a sample of Italian adults with BDZ dependence in relation with their QTc prolongation risk. We used Latent Class Analysis (LCA) on data collected from 251 inpatients of the Addiction Medicine Unit in Verona to group patients into three classes according to their substance use and their QTc prolongation risk. Results showed no significant relationship between QTc prolongation and BDZ use in any of the classes considered. We conclude that BDZs, even if used long-term and at high dosages, can be considered safe in terms of cardiovascular complications for patients., (© 2024. The Author(s).)

In the last years, only few studies in literature have focused on the use and abuse of benzodiazepines (BZDs) in sport. Benzodiazepine-related problems include misuse, addiction, driving impairments, and morbidity and mortality related to overdose and withdrawal. Two clinical cases regarding elite endurance athletes evidenced that they had started to use BZDs to counteract insomnia, to recover faster from training sessions and to manage muscle pain. One of the important points that emerged from their stories was that their sports doctors did not recognize the drugs' addictive properties, and did not intervene to gradually reduce the dosage. Experts have previously provided recommendations for BZD therapy management in clinical practice. In this article, we would like to address sports medicine physicians specifically and provide guidelines to help them manage situations involving BZD prescription, the recognition of addiction, and intervention strategies., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Zandonai, Peiró, Fusina, Lugoboni and Zamboni.)

Zolpidem is indicated in cases of severe insomnia in adults and, as for BDZs, its assumption should be limited to short periods under close medical supervision. Since several drugs cause corrected QT interval (QTc) elongation, the authors investigated whether high daily doses of Zolpidem could cause QTc elongation. The study was conducted in the Addiction Medicine Unit of the G.B. Rossi University Hospital in Verona. The data were collected from hospitalizations carried out between January 2015 and February 2020 and refer to a total of 74 patients, 38 males and 36 females, who were treated for detoxification from high doses of Zolpidem with the "Verona Detox Approach With Flumazenil." One patient out of 74 had QTc elongation (479 ms). The patient was male and took a daily dose of 50 mg of Zolpidem; he did not take concomitant therapies that could cause QTc lengthening. He had no electrolyte alterations, no contemporary or previous intake of barbiturates, heroin, cocaine, THC, alcohol, NMDA or nicotine which could cause an elongation of the QTc interval. The present study highlights the low risk of QTc elongation due to high dosages of Zolpidem; however, if, on one hand, we can affirm that Zolpidem is a safe drug, on the other, the widespread use of high dosages of this drug for prolonged periods of time is problematic and worrying., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Campagnari, Zamboni, Fusina, Casari and Lugoboni.)

Benzodiazepine (BDZ) abuse, especially concerning high doses of BDZs, is an impairing substance use disorder (SUD) that is often difficult to treat. Craving and cue reactivity (CR) are two important phenomena that have a prominent role in maintaining addiction and triggering relapses in BDZ abuse; nevertheless, they have rarely been addressed in scientific literature. The present study aims to fill these gaps by implementing a highly innovative virtual reality (VR) design to assess the impact of substance-related environmental cues on BDZ craving, as well as their influence on patients' affective states. Therefore, on one hand, this research will contribute to the assessment of VR feasibility in the study of these phenomena, and, on the other, it will help disentangle the role that CR and craving have on mood and attention, which are equally important factors to consider when treating SUDs. We will recruit a healthy control group and a patient group comprising people seeking treatment for BDZ detoxification. The experimental design will consist of the presentation of three VR scenarios, one neutral, one BDZ-related but without BDZ cues, and another with BDZ cues. The craving will be measured through a virtual analog scale (VAS); the Profile of Mood States (POMS) and Alcohol Attention Scale (AAS) questionnaires in a modified version will also be administered. We will additionally control for VR-induced feelings of sickness by administering the Simulator Sickness Questionnaire (SSQ), and the Presence Questionnaire (PQ) will be used to investigate participants' sense of presence in virtual environments. We expect patients to exhibit higher levels of craving, and that the craving will be higher after exposure to a cue-related virtual environment as compared to a neutral scenario., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Zamboni, Toldo, Fusina, Mattiello, Mannari, Campagnari, Schiavone, Congiu, Verlato, Chiamulera and Lugoboni.)

Nicotine addiction is a widespread, worldwide epidemic, causing six million deaths per year. A large variety of treatments for smoking cessation are currently available, including Cytisine, which is a promising drug due to its low cost and high safety levels. Notwithstanding the important amount of research on tobacco addiction treatments, smoking remains one of the most difficult substance use disorders to treat, probably also due to the fact that pharmacological treatment often overlooks other maintaining factors in this addiction, such as sensory impact and cue reactivity. To address this gap in both treatment protocols and scientific literature, we propose a study protocol in which we will compare the effects of combining Cytisine with Nirdosh, a herbal tobacco substitute, to Cytisine only in two groups of patients (C + N and C) who will also undergo exposure to four different virtual reality settings that will assess the importance of environmental cues. We will further assess mood and craving in the two samples, and include a control group taken from the general population. We expect the C + N group to report a more positive mood and a lower sensitivity to tobacco-related environmental cues., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Zamboni, Campagnari, Giordano, Fusina, Carli, Congiu, Barbon, Melchiori, Casari, Tedeschi, Vesentin, Verlato, Infante and Lugoboni.)

Vaccination against COVID-19 is crucial in the attempt of containing the virus' spread, but facing a viral pathogen with such a high prevalence means that vaccination strategies are facing an unprecedented situation. People that use illicit drugs may have elevated risk of adverse outcomes from COVID-19 given their high prevalence of underlying medical conditions, including respiratory and pulmonary disease, chronic liver disease, cardiovascular and cerebrovascular conditions, diabetes, and compromised immune systems. Despite a widespread distribution on the Italian territory, a large presence of health personnel and a long-standing experience in vaccinations, addiction clinics have yet to be involved in the vaccination campaign against COVID-19. The aim of this study was to investigate the beliefs of drug users attending some Italian addiction clinics, in order to envisage any vaccine administration strategies involving the services themselves. A questionnaire used for the Italian general population to investigate the relative importance of some factors in influencing the propensity to vaccinate against COVID-19, was administrated to drug users in a multicenter survey. The majority of respondents expressed general confidence in vaccines and a good willingness to undergo vaccination. Given strong peer networks, high coverage of treatment and harm reduction interventions, Italian public addiction clinics could play a strategic role in administering the vaccine in this hard-to-reach population, usefully aiding the global campaign against the virus., Competing Interests: Declaration of conflicting interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2022.)

Cytisine is considered to be the oldest medication for smoking cessation and has been used for this purpose in some Eastern/Central European and Central Asian countries for over 50 years. Several sources points towards cytisine's efficacy and effectiveness; it's well tolerated when taken at the recommended dose, and adverse events reported in trials are typically non-serious and self-limiting gastrointestinal and sleep disturbances. We report a suspect case of urticaria during treatment for smoking cessation with cytisine in a woman of 48 years treated for smoking at the Unit of Addiction Medicine, Department of Internal Medicine, Hospital Trust of Verona, Italy.  The therapeutic protocol of cytisine that was used is of the "inductive" type; it consists in gradually increasing the daily capsules taken, with a parallel reduction in the number of cigarettes smoked until complete cessation between the fifth and ninth day of therapy (quit day) The number of capsules taken is then gradually reduced. She was treated for the firsts three days with betamethasone 1 mg/die, on the advice of her general practitioner, and suspended Cytisine. A week later the patient showed signs of recovery.

Cognitive behavioral therapy (CBT) is the most successful protocol in gambling disorder (GD) treatment. However, it presents some weaknesses, especially concerning relapse prevention (RP). RP is one of the most important therapeutic steps, aiming at managing cravings and to avoid future relapse increasing perceived self-efficacy. Encouraging results come from the blending of psychotherapy and virtual reality (VR), containing gambling cues. The goal of Alter Game (approved by the Ethical Commission, Prot. No. 69346) is verifying the efficacy of an innovative psychological treatment for GD based on the integration of traditional CBT therapy and an immersive VR cue exposure therapy using a serious virtual game, which is a game designed for purposes other than entertainment. RP in virtual cue-exposure therapy allows pathological gamblers to manage the urge to gamble and to avoid relapse by becoming aware of which internal and external triggers are related to craving. We hypothesize that the integrated intervention will be more effective than simple CBT with regard to self-efficacy, craving, and gambling-related distortions. Four virtual ecological environments were developed, and a virtual app, Exludo, interfaced with a computerized multiparametric acquisition system for biofeedback, was created. A sample of about 60 patients aged between 18 and 65 with GD referring to the Addiction Medicine Unit of Verona (Rossi Hospital) will be recruited. Patients will be randomly assigned to the CBT group (16 CBT sessions) or the CBT + VR group (8 CBT sessions + 8 VR cue-exposure therapy sessions). The MCMI-III, the BIS-11, and the SOGS will be used to evaluate inclusion and exclusion criteria, while the Gambling Related Cognitions Scale and the Multidimensional Gambling Self-Efficacy Scale will be used to verify changes as a function of the treatment. Craving will be evaluated through VAS, and psychophysiological variables will be assessed through biofeedback. A pre-test/post-test experimental design with a 1-month follow-up will be conducted. This study will examine an innovative psychotherapeutic protocol for GD treatment, and it will help in identifying new virtual tools to increase the efficacy of traditional therapeutic approaches that could also be applied to treat other addictions., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Giordano, Donati, Zamboni, Fusina, Primi and Lugoboni.)

Introduction: Since the 1990s there has been evidence of the significant role Flumazenil (FLU) has in benzodiazepines (BZD) detoxes. The Verona Detox approach has been developed for high dose BZD and Z-drug detoxification via continuous subcutaneous infusion of FLU, a selective BZD receptor antagonist acting on the BZD subunit of the GABA-A receptor. Flumazenil is licensed in the United Kingdom and other countries to treat only BZD overdose although numerous studies have demonstrated its effectiveness in rapidly resetting GABA-A receptors, quickly reducing tolerance and dependence from BZD, and providing a safe and rapid detox from benzodiazepines., Objective: The aim of this article is to provide all healthcare professional who are interested in BZD detoxification with an approach and clear practical information on how to administer FLU., Method: In this article we outline the approach in detail, describing all medical and nursing procedures day by day. This detox treatment is indicated for patients abusing from at least 5 Defined Daily Dose (DDD) of BZDs or Z-drugs. The process lasts 7 days, and is conducted under medical supervision (daily reviews) and continuous nursing (24/7). During this period, 7mg of FLU is administered (1 mg/24) through an elastomeric pump, via continuous subcutaneous infusion., Conclusion: To this day, the largest database of FLU detoxification was published by our group, showing how this treatment is safe, with very little side effects even in patients with significant medical comorbidities., Competing Interests: AM was employed by Camden and Islington NHS Foundation Trust. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Casari, Metastasio, Zamboni, Biasioli, Campagnari and Lugoboni.)