Hepatitis A Virus among Drug Users and the Role of Vaccination: A Review

In countries with advanced economies better health and hygiene conditions, along with the introduction, in some cases, of global vaccination, have relegated most viral hepatitis to marginal social groups and, in particular, drug users (DUs). The availability of safe and effective vaccines for hepatitis A virus (HAV) and B (HBV) may play a major role in combating this phenomenon. Despite the availability of a safe and effective vaccine for over a decade and the recommendations of international health organizations, vaccinations against HAV among DUs are not as widely known and available as are HBV vaccinations. The purpose of this review article is to present the most significant data in the literature on the prevalence of HAV among DUs and the role of targeted vaccination. To our knowledge, the present article is the first to solely deal with vaccination against HAV in DUs. Immunization after the administration of anti-HAV vaccine has been demonstrated in DUs even if they have responded significantly less than either the general population or carriers of chronic liver disease. All the vaccines were well tolerated and adherence to the vaccine schedule was good. Further studies are needed to optimize the timing and doses of vaccine to be administered to DUs, especially to assess adherence and antibody persistence. Vaccination campaigns are feasible among DUs and have proven to be highly cost–effective

Non-invasive brain stimulation for gambling disorder: a systematic review

Background:Gambling disorder (GD) is the most common behavioral addiction and shares pathophysiological and clinical features with substance use disorders (SUDs). Effective therapeutic interventions for GD are lacking. Non-invasive brain stimulation (NIBS) may represent a promising treatment option for GD. Objective:This systematic review aimed to provide a comprehensive and structured overview of studies applying NIBS techniques to GD and problem gambling. Methods:A literature search using Pubmed, Web of Science, and Science Direct was conducted from databases inception to December 19, 2019, for studies assessing the effects of repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (t-DCS) on subjects with GD or problem gambling. Studies using NIBS techniques on healthy subjects and those without therapeutic goals but only aiming to assess basic neurophysiology measures were excluded. Results:A total of 269 articles were title and abstract screened, 13 full texts were assessed, and 11 were included, of which six were controlled and five were uncontrolled. Most studies showed a reduction of gambling behavior, craving for gambling, and gambling-related symptoms. NIBS effects on psychiatric symptoms were less consistent. A decrease of the behavioral activation related to gambling was also reported. Some studies reported modulation of behavioral measures (i.e., impulsivity, cognitive and attentional control, decision making, cognitive flexibility). Studies were not consistent in terms of NIBS protocol, site of stimulation, clinical and surrogate outcome measures, and duration of treatment and follow-up. Sample size was small in most studies. Conclusions:The clinical and methodological heterogeneity of the included studies prevented us from drawing any firm conclusion on the efficacy of NIBS interventions for GD. Further methodologically sound, robust, and well-powered studies are needed

Venlafaxine dependence in a patient with a history of alcohol and amineptine misuse

ABSTRACT Background Venlafaxine is an inhibitor of neuronal serotonin and noradrenaline re-uptake and a weak inhibitor of dopamine re-uptake. There was no indication of problems of abuse/dependence during the clinical trials. Case description A 53-year-old client with a history of alcohol and amineptine misuse and a long history of recurrent depression, for which he was prescribed venlafaxine tablets. Over time, he increased the dosage to 50 tablets daily (3750 mg). Large venlafaxine dosages produced amphetamine-like effects, due possibly to the related increase in dopamine turnover. Once hospitalized for detoxification, the patient had a symptomatology which was consistent with a serotonergic discontinuation syndrome. Conclusions Physicians should be aware that patients with a history of drug and alcohol abuse might develop venlafaxine dependence

Adult attention-deficit/hyperactivity disorder symptoms, cognitive dysfunction and quality of life in high-dose use of benzodiazepine and Z-drug

High-dose use of benzodiazepines (BZDs) and Z-drugs was found to be associated with adult attention deficit/hyperactivity disorder (ADHD) and multidomain cognitive deficits, but the interplay between these factors and its effect on quality of life (QoL) is unclear. We explored (a) whether cognitive dysfunction differs in high-dose BZD/Z-drug users with and without adult ADHD and (b) the impact of cognitive deficits and adult ADHD on QoL in this substance-use disorder (SUD). From January 2015 to December 2019, we recruited 207 high-dose BZD/Z-drug users seeking treatment. We assessed the presence of adult ADHD with a screening tool, which was validated in SUD patients, and collected demographic, clinical and QoL data from the 76 included patients. A neuropsychological battery explored five cognitive domains. We found that: (a) screening for adult ADHD was frequently positive; (b) Short Form-36 (SF-36), a self-administered QoL questionnaire, was worse than the general population and worse in patients positive (ADHD+) vs. those negative (ADHD-) to ADHD screening tool; (c) executive function was significantly worse in ADHD+than ADHD- patients; (d) some SF-36 dimensions were negatively influenced by executive dysfunction; (e) multivariate analysis showed an interplay between adult ADHD and cognitive dysfunction in worsening QoL. We documented a complex interplay between adult ADHD, cognitive dysfunction and QoL in high-dose BZD/Z-drug users. Assessing adult ADHD, neuropsychological measures and QoL may offer a full scenario of these patients, who are frequently impaired in everyday activities. Future research should explore whether pharmacological treatment might improve cognitive dysfunction and QoL in this SUD

Continuous Infusion of Flumazenil in the Management of Benzodiazepines Detoxification

An effective approach in the treatment of benzodiazepine (BZD) overdosing and detoxification is flumazenil (FLU). Studies in chronic users who discontinued BZD in a clinical setting suggested that multiple slow bolus infusions of FLU reduce BZD withdrawal symptoms. The aim of this study was to confirm FLU efficacy for reducing BZD withdrawal syndrome by means of continuous elastomeric infusion, correlated to drugs plasma level and patients\u2019 compliance. Methods: Seven-day FLU 1 mg/day subcutaneously injected through an elastomeric pump and BZDs lormetazepam, clonazepam, and lorazepam were assessed by HPLC-MS/MS in serum of patients before and after 4 and 7 days of FLU continuous infusion treatment. Changes in withdrawal severity were assessed by using the BZD Withdrawal Scale (BWS). Results: Fourteen patients (mean age \ub1 SD 42.5 \ub1 8.0 years, 5 male and 9 female), admitted to the hospital for high-dose BZD detoxification, were enrolled in the study. Serum FLU concentrations significantly decreased from 0.54 \ub1 0.33 ng/ml (mean \ub1 SD) after 4 days of treatment to 0.1 \ub1 0.2 ng/ml at the end of infusion. Lormetazepam concentrations were 502.5 \ub1 610.0 ng/ml at hospital admission, 26.2 \ub1 26.8 ng/ml after 4 days, and 0 at the end of treatment. BWS values decreased during FLU treatment temporal period. FLU was well-tolerated by patients. Conclusions: Elastomeric FLU infusion for BZD detoxification is a feasible administration device to maintain adequate, constant, and tolerated FLU concentrations for reducing BZD withdrawal symptoms

High-dose dependence and cognitive side effects to medical prescription of etizolam

Introduction: The use of novel designer drugs has increased worldwide over the years. Etizolam is a designer benzodiazepine (BZD) that has raised concern because of its growing non-medical use, liability to tolerance and dependence, and related harms. Studies exploring the abuse liability and cognitive effects of etizolam outside the therapeutic doses are lacking.Aims: To explore the abuse liability of etizolam and the characteristics of patients affected by etizolam high-dose dependence in a nationwide tertiary referral addiction unit. To document the cognitive changes to etizolam high-dose use.Design and Methods: Sociodemographic and clinical data on subjects with etizolam high-dose use were retrospectively collected from a database of 1,293 patients consecutively admitted to the Addiction Medicine Unit, Verona University Hospital, Italy for detoxification from high-dose BZDs or Z-drugs dependence. Thorough neuropsychological testing explored the cognitive side effects of high-dose etizolam use.Results: We found eleven etizolam high-dose users, of which eight used etizolam only, and three used etizolam with other BZDs/zolpidem. All the patients were prescribed etizolam for medical reasons, i.e., anxiety and/or insomnia. Neuropsychological evaluation showed deficits of working memory, visuospatial memory and executive function in a 27-year-old woman who used etizolam 15 mg daily.Discussion: Our findings suggest that abuse and dependence liability of etizolam should be considered a public health and social problem. They offer preliminary evidence on the cognitive side effects of etizolam high-dose use.Conclusions: This report offers new information on the potential harms of etizolam in patients who are prescribed this drug for medical reasons

COVID-19 lockdown: impact on online gambling, online shopping, web navigation and online pornography

Background: The COVID-19 pandemic and control measures may have had an impact on unpleasant emotions experimented during the lockdown (LD). This may have increased the number of hours spent online and could have impacted the quality of the enacted behavior, in terms of loss of control of Internet use. In this online survey, we were interested in measure how much loss of control was perceived regarding online gambling, online shopping, the fruition of online pornographic content and web navigation.Design and methods: The online survey was carried out during the COVID-19 pandemic in the post-lockdown and 1232 subjects participated in the survey. In the participating sample, healthcare workers (HW) were 43.1% of the sample, of which 18.7% were directly involved in the Coronavirus emergency, and 52.3% of the sample is not a HW. Only 0.6% of the sample gambled online and 37.5% of those reported losing control of their gambling mode. Most of the sample shopped online during the LD (70.1%), but only 7.2% of those lost control by buying and/or spending more than what they had set themselves.Results: Significant data emerged showing that those who lost control while online shopping also lost control regarding the amount of time spent online (p<0.001); 21.6% of the sample, reported making use of online pornographic material during LD, 4.7% of them stated that the frequency increased and 5.1% reported losing control by having spent more money or more time than what was intended. Finally, 44.7% of the sample have experienced loss of control during the web navigation. Furthermore, during the LD 67.8% of the sample reports having experienced unpleasant emotions. Of these, 8.4% state that they enacted behaviors such as online gambling, online shopping, online pornographic material viewing and web navigation to counter their negative emotions. Interestingly, we found a correlation between loss of control during web navigation and online shopping and the emotional states “upset”, “scared” and “restless” (p<0.05).Conclusion: To conclude, there was no significant increase in potentially addictive behaviors, nor an increase in loss of control of these behaviors when enacted online. However, the loss of control in online shopping and web navigation was significantly correlated to the unpleasant emotional states of nervousness, fear and restlessness, whereas those who reported feeling strong and able to handle the situation experienced a lower loss of control in their web navigation. These correlations may suggest that these online behaviors may act as modulators of unpleasant emotional states

Detoxification improves multidomain cognitive dysfunction in high-dose benzodiazepine abusers

Purpose: High-dose benzodiazepines (BZDs) abuse has been documented to cause multidomain cognitive dysfunction. We explored whether cognitive abnormalities to high-dose BZD abuse might be reversed by detoxification with slow subcutaneous infusion of flumazenil. Methods: We recruited 96 patients consecutively admitted to the Department of Internal Medicine, Addiction Medicine Unit, Verona University Hospital, Italy for detoxification from high-dose BZD dependence. After selection for inclusion and exclusion criteria, 50 patients (23 men, 27 women; age 42.7 \ub1 10.3 years) were included. They underwent a comprehensive neuropsychological battery to explore verbal memory, visuospatial memory, working memory, attention, and executive functions 28-30 days prior to admission for detoxification (T0) and at the end of detoxification, i.e., 7 days after admission (T1). A group of 50 healthy adults (24 men, 26 women; mean age 44.5 \ub1 12.8 years) matched for age, sex, and education served as controls. Results: At T0, patients scored significantly worse than healthy controls in all the neuropsychological tests. Depression and anxiety scores were associated with impaired verbal memory at T0 in patients. T1-T0 comparison showed improved performances in all neuropsychological tests after the end of detoxification in patients. Conclusion: We confirmed that all neuropsychological domains were significantly and profoundly impaired by high-dose BZD abuse and documented that cognitive abnormalities improved after detoxification with slow subcutaneous infusion of flumazenil

Polysubstance use patterns among high dose benzodiazepine users: a latent class analysis and differences between male and female use

Benzodiazepines (BZDs) represent one of the most widely used groups of pharmaceuticals, but if used for long periods of time they are associated with dependence and an increased risk of harmful effects. High-dose (HD) BZD dependence is a specific substance use disorder associated with a poor quality of life. It is especially important to pinpoint differences in HD BZD addict subgroups in order to tailor treatment to the individual's specific needs, also considering possible comorbidities with other substance use disorders. We conducted a study to evaluate HD BZD dependence (converted doses to diazepam equivalents, mg) in an Italian sample of 1,354 participants. We also investigated if and to which extent participants co-used other substances (alcohol, tobacco, cannabis/cannabinoids, cocaine, and heroin). We then performed latent class analysis (LCA) to identify the use patterns of these substances, finding three classes: participants in Class 1 (4.3% of the sample) had the highest probability of also using cocaine and alcohol (Polysubstance BZD users); Class 2 comprised subjects with the highest probability of being former heroin, cocaine, THC, and alcohol users (Former polysubstance BZD users); Class 3 represented mono-dependence BZD users (78.5% of the sample) and was the most prevalent among women, while young men were most prevalent in Class 1. The present study underlines different characteristics in HD BZD users both concerning other addictions and sex, and also highlights the need for a stricter control of BZD use, ranging from prescriptions to sales