Assessing the 2004-2018 fentanyl misusing issues reported to an international range of adverse reporting systems

© 2019 Schifano, Chiappini, Corkery and Guirguis. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. Submitted 2 October 2018, Accepted 14 January 2019, published 1 February 2019.Objective: A recent, global, increase in the use of opioids including the prescribing, highly potent, fentanyl has been recorded. Due its current popularity and the potential lethal consequences of its intake, we aimed here at analyzing the fentanyl misuse, abuse, dependence and withdrawal-related adverse drug reactions (ADRs) identified within the European Medicines Agency (EMA), the United Kingdom Yellow Card Scheme (YCS), and the United States Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) databases. Methods: Descriptive analysis of both ADRs and related cases. Results: The analysis of fentanyl-related misuse, abuse, dependence and withdrawal cases reported during years 2004-2018 to the EMA, the YCS, and the FAERS showed increasing levels overtime, specifically, EMA-related data presented two peaks (e.g., in 2008 and 2015), whilst the FAERS dataset was characterized by a dramatic increase of the ADRs collected over the last 18 months, and particularly from 2016. Some 127,313 ADRs (referring to n = 6,161 patients/single cases) related to fentanyl's misuse/abuse/dependence/withdrawal issues were reported to EMA, with 14,287 being judged by the reporter as "suspect." The most represented ADRs were: "drug dependence "(76.87%), "intentional product misuse" (13.06%), and "drug abuse" (7.45%). Most cases involved adult males and the concomitant use of other prescribing/illicit drugs. A range of idiosyncratic (i.e., ingestion/injection of transdermal patches' fentanyl) and very high-dosage intake cases were here identified. Significant numbers of cases required either a prolonged hospitalization (192/559 = 34.35%) or resulted in death (185/559 = 33.09%). Within the same time frame, YCS collected some 3,566 misuse/abuse/dependence/withdrawal ADRs, corresponding to 1,165 single patients/cases, with those most frequently reported being "withdrawal," "intentional product misuse," and "overdose" ADRs. Finally, FAERS identified a total of 19,145 misuse/abuse/dependence/withdrawal-related cases, being "overdose," withdrawal, and "drug use disorder/drug abuse/drug diversion" the most represented ADRs (respectively, 43.11, 20.80, and 20.29%). Conclusion: Fentanyl abuse may be considered a public health issue with significant implications for clinical practice. Spontaneous pharmacovigilance reporting systems should be considered for mapping new trends of drug abuse.Peer reviewe

On the Consequences of State Dependent Preferences for the Pricing of Financial Assets

This paper introduces state dependent utility into the standard Mehra and Prescott (1985) economy by allowing the representative agent's coefficient of relative risk aversion to vary with the underlying economy's growth rate. Existence of equilibrium is proved and its asymptotic properties analyzed. This generalization leads to level dependent marginal rates of substitution, a property that sharply distinguishes this model from the standard construct. For very low coefficients of relative risk aversion, the equilibrium risk free and risky security returns are demonstrated to have volatilities and an associated equity premium that substantially exceed what is found in the data. This provides a contrasting perspective on the classic "equity premium puzzle."state dependent utility; equity premium; equity premium puzzle

COVID-19: The hidden impact on mental health and drug addiction

© 2020 Chiappini, Guirguis, John, Corkery and Schifano. 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 use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.There is concern the Coronavirus Disease (COVID)-19 pandemic is having a negative impact on the mental health of the general population through a range of suggested mechanisms: fear, uncertainty, and anxiety; social distancing/isolation; loneliness; and economic repercussions (1–3). Previous disasters such as the Severe Acute Respiratory Syndrome (SARS) in 2003 (4–6) contributed to increased anxiety, mood, and thought disorders, adjustment disorders, and post-traumatic stress disorders (PTSD) (1, 7–15), resulting, in extreme cases, in suicidal behaviours (e.g., suicidal ideation, suicide attempts, and actual suicide) (10, 16), especially in cases of concomitant Substance Use Disorder (SUD) (17, 18). According to a recent study from the Well Being Trust (18) the high levels of stress, isolation and unemployment due to the COVID-19 pandemic could cause up to 75,000 “deaths of despair” related to deaths to drug, alcohol, and suicide (18). High risk of mental illness was previously identified in individuals with existing or history of mental illnesses (1, 9, 12, 14, 19), but also vulnerable categories might be considered the elderly (>80 years old), children/adolescents, individuals from deprived areas, peri-natal women and BAME (Black, Asian and minority ethnicities) (1, 12, 14, 19). Finally, healthcare workers have been experiencing emotional overload due to several reasons, including both organizational issues relating to the shortage of suitable personal protective equipment, reduction in human resources and relentless work shifts (20–23), but also the burden developed by the fear of becoming infected and infecting relatives, high mortality rates, grieving the loss of patients and colleagues, separation from families (22–24). Specifically, according to Huang et al. (25), among the first-line medical staff of a Tertiary Infectious Disease Hospital for COVID-19 in China, the incidence of anxiety and post traumatic symptoms in female medical staff was higher than that in male, and in nurses more represented than that in doctors (25).Peer reviewe

Recent Changes in Drug Abuse Scenario: The Novel Psychoactive Substances (NPS) Phenomenon

copyright 2019 by the authors. Articles in this book are Open Access and distributed under the Creative Commons Attribution (CC BY) license, which allows users to download, copy and build upon published articles, as long as the author and publisher are properly credited, which ensures maximum dissemination and a wider impact of our publications. The book as a whole is distributed by MDPI under the terms and conditions of the Creative Commons license CC BY-NC-ND.Final Published versio

Beyond the ‘purple drank’: Study of promethazine abuse according to the European Medicines Agency adverse drug reaction reports

Submitted 30 April; revisions submitted 17 July 2020; accepted 8 August 2020; first published 10 January 2021.Background: Promethazine is a medicinal product, available on its own or in combination with other ingredients including dextromethorphan, paracetamol, and/or expectorants. Anecdotal reports have however indicated that promethazine may have a misuse potential, especially in adolescents. Objective: We aimed at studying how this phenomenon has been reported to the European Monitoring Agency (EMA) Adverse Drug Reactions (ADRs) database. Methods: After a formal request to the EMA, the promethazine-specific dataset has been studied performing a descriptive analysis of the misuse/abuse/dependence related-ADR reports. The study was approved by the University of Hertfordshire (LMS/PGR/UH/03234). Results: The analysis of promethazine data showed increasing levels of misuse/abuse/ dependence issues over time (2003-2019). Out of a total number of 1,543 ADRs’ cases, the abuse/misuse/dependence-related cases reported were 557, with ‘drug abuse’ (300/557: 53.8%) and ‘intentional product misuse’ (117/557: 21.0%). being the most represented ADRs. A high number of fatalities were described (310/557: 55.6%), mostly recorded as ‘drug toxicity/drug abuse’ cases, with opiates/opioids having been the most commonly reported concomitant drugs used. Conclusion: Anecdotal promethazine misuse/abuse reports have been confirmed by EMA data. Promethazine misuse/abuse appears to be an alarming issue, being associated with drug-related fatalities. Thus, healthcare professionals should be warned about a possible misuse of promethazine and be vigilant, as in some countries medicinal products containing promethazine can be purchased over the counter. Since promethazine is often available in association with opioids, its abuse may be considered a public health issue, with huge implications for clinical practice.Peer reviewe

Focus on Clozapine Withdrawal- and Misuse-Related Cases as Reported to the European Medicines Agency (EMA) Pharmacovigilance Database

© 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).Background: Clozapine is of high clinical relevance for the management of both treatment-resistant schizophrenia and psychotic disturbances with concurrent drug misuse. Although the molecule presents with a range of well-known side-effects, its discontinuation/withdrawal syndrome has been only anecdotally described. Aims: the 2005–2018 European Medicines Agency (EMA) dataset of Adverse Drug Reactions (ADRs) was analyzed to identify and describe possible clozapine withdrawal-and misuse-/abuse-/dependence-related issues. Method: A descriptive analysis of clozapine-related ADRs was performed when available, data on ADRs’ outcome, dosage, and possible concomitant drug(s) were considered. Results: Out of 11,847 clozapine-related ADRs, some 599 (5.05%) were related to misuse/abuse/dependence/withdrawal issues, including 258 withdrawal-related (43.1%); 241 abuse-related (40.2%); and 80 intentional product misuse-related (13.3%) ADRs. A small number of overdose-and suicide-related ADRs were reported as well. Clozapine was typically (69.2%) identified alone, and most (84.7%) fatalities/high-dosage intake instances were reported in association with a history of substance abuse. Conclusions: Previous suggestions about the possibility of a clozapine discontinuation/withdrawal occurrence are here supported, but further studies are needed. However, the misuse/abuse cases here identified might be difficult to interpret, given the lack of studies highlighting the possible recreational use of clozapine. The high-dosage intake, fatal outcomes and clozapine/polydrug abuse issues reported here may, however, be a reason for concern.Peer reviewedFinal Published versio

An investigation into the relationship(s) between the different chemical classes of synthetic cathinones and their effects: desired, adverse and toxic

Final Published versio

COVID-19 Pandemic Impact on Substance Misuse: A Social Media Listening, Mixed Method Analysis

© 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). Submitted to Brain Sciences Manuscript ID: brainsci-1275549 on 10 June 2021. Reviewers’ comments received 23 June 2021. Revisions submitted 2 July 2021. Accepted 5 July 2021. Published online 9 July 2021. https://doi.org/10.3390/brainsci11070907 (registering DOI)The restrictive measures adopted during the COVID-19 pandemic modified some previously consolidated drug use patterns. A focus on social networks allowed drug users to discuss, share opinions and provide advice during a worldwide emergency context. In order to explore COVID-19-related implications on drug trends/behaviour and on most popular psychotropic substances debated, the focus here was on the constantly updated, very popular, Reddit social platform’s posts and comments. A quantitative and qualitative analysis of r/Drugs and related subreddits, using a social media listening netnographic approach, was carried out. The post/comments analysed covered the time-frame December 2019–May 2020. Between December 2019 and May 2020, the number of whole r/Drugs subreddit members increased from 619,563 to 676,581 members, respectively, thus increasing by 9.2% by the end of the data collection. Both the top-level r/Drugs subreddit and 92 related subreddits were quantitatively analysed, with posts/comments related to 12 drug categories. The drugs most frequently commented on included cannabinoids, psychedelics, opiates/opioids, alcohol, stimulants and prescribed medications. The qualitative analysis was carried out focussing on four subreddits, relating to some 1685 posts and 3263 comments. Four main themes of discussion (e.g., lockdown-associated immunity and drug intake issues; drug-related behaviour/after-quarantine plans’ issues; lockdown-related psychopathological issues; and peer-to-peer advice at the time of COVID-19) and four categories of Redditors (e.g., those continuing the use of drugs despite the pandemic; the “couch epidemiologists”; the conspirationists/pseudo-science influencers; and the recovery-focused users) were tentatively identified here. A mixed-methods, social network-based analysis provided a range of valuable information on Redditors’ drug use/behaviour during the first phase of the COVID-19 pandemic. Further studies should be carried out focusing on other social networks as well as later phases of the pandemic.Peer reviewe

Exploring the baseline knowledge and experience of healthcare professionals in the United Kingdom on Novel Psychoactive Substances

Submitted 28 january 2020. Reviwers' comments received 11 February 2020. Accepted 26 February 2020. Published 2 March 2020.Objective: This survey aimed to explore knowledge and experience on novel psychoactive substances (NPS) of healthcare professionals (HCPs). The study also aimed to assess how HCPs would like to improve their knowledge of NPS. Methods: Seventy paper questionnaires were disseminated in 2017 within continuing education events to pharmacists, nurses and general practitioners (GPs). Additionally, 127 online surveys were completed using the Qualtrics platform by other HCPs and mental health nurses in six United Kingdom (UK) independent mental health hospitals long-stay in-patient rehabilitation services. Two educational sessions involving pharmacists and GPs were also held in late 2017 and mid-2018. Knowledge of NPS by HCPs was evaluated prior to the start of the educational events. Evaluation forms were handed out post-sessions to garner feedback, especially on areas for improvement for future sessions. Statistical analysis of data was undertaken using SPSS (V.25). Results: Most HCPs reported only 'basic' to 'intermediate' NPS knowledge. Substance misuse service staff felt more informed, were more often consulted and had greater confidence regarding NPS compared to hospital and primary care professionals. A negative association was found between the age of the HCP and knowledge of NPS. Most participants expressed a need for regular training and updates as insufficient NPS-related information is currently received. Conclusions: An improvement within the self-reported knowledge of HCPs on NPS is evident in comparison to previous studies. Continued education of HCPs on NPS is fundamental for the provision of improved harm reduction services, which can enhance overall care for NPS service users.Peer reviewedFinal Published versio

On the Consequences of State Dependent Preferences for the Pricing of Financial Assets

This paper introduces state dependent utility into the standard Mehra and Prescott (1985) economy by allowing the representative agent’s coefficient of relative risk aversion to vary with the underlying economy’s growth rate. Existence of equilibrium is proved and its asymptotic properties analyzed. This generalization leads to level dependent marginal rates of substitution, a property that sharply distinguishes this model from the standard construct. For very low coefficients of relative risk aversion, the equilibrium risk free and risky security returns are demonstrated to have volatilities and an associated equity premium that substantially exceed what is found in the data. This provides a contrasting perspective on the classic “equity premium puzzle.”state dependent utility; equity premium; equity premium puzzle