Is there a potential of misuse for venlafaxine and bupropion?

© 2018 Schifano and Chiappini. 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 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.Objective: Traditionally, studies on the nonmedical use of pharmaceutical products have focused on controlled substances; e.g. opiates/opioids; and benzodiazepines. Although both bupropion and venlafaxine have been reported as being misused, only anecdotal reports have been made available so far. Hence, the European Monitoring Agency (EMA) Adverse Drug Reactions (ADRs), misuse/abuse/dependence and withdrawal, venlafaxine- and bupropion-related, database was here analyzed. Methods: All EMA spontaneous reports relating to venlafaxine (2005-2016) and bupropion (2003-2016) notifications were here analyzed, to provide a descriptive analysis by source, gender, age, and type of report. The UK-based, 2000-2016, Yellow Card Scheme pharmacovigilance database, bupropion and venlafaxine withdrawal reports were compared as well with those pertaining to fluoxetine and paroxetine. Results: Out of 20,720 (bupropion) and 47,516 (venlafaxine) total number of ADRs, some 2,232 (10.8%), and 4,071 (8.5%) misuse/abuse/dependence ADRs were respectively associated with bupropion and venlafaxine. Conversely, bupropion withdrawal-related ADRs were here reported in 299/20,720 (1.44%) cases and in 914/47,516 (1.92%) cases for venlafaxine. Overall, all bupropion and venlafaxine misuse-/abuse-/dependence- and withdrawal-ADRs were related to a respective number of 264 and 447 patients. According to the Proportional Reporting Ratio (PRR) computation, in comparison with venlafaxine bupropion resulted to be more frequently misused/abused (PRR: 1.50), but less frequently associated with both dependence (PRR: 0.92) and withdrawal (PRR: 0.77) issues. Yellow Card Scheme data suggested that paroxetine and venlafaxine, in comparison with fluoxetine and bupropion, were associated with higher number of withdrawal-related reports. Conclusions: The dopaminergic, stimulant-like, bupropion activities may be associated with its possible recreational value. Present data may confirm that the occurrence of a withdrawal syndrome may be a significant issue for venlafaxine-treated patients.Peer reviewedFinal Published versio

Schooling for violence and peace : how does peace education differ from ‘normal’ schooling?

This article reviews literature on the roles of schooling in both reproducing and actively perpetrating violence, and sets out an historical explanation of why schools are socially constructed in such a way as to make these roles possible. It then discusses notions of peace education in relation to one particular project in England before using empirical data from research on the project to examine contrasts between peace education approaches and ‘normal’ schooling from the viewpoints of project workers, pupils and teachers. It concludes that such contrasts and tensions do indeed exist and that this raises serious questions about the compatibility of peace education and formal schooling

Zircon ages in granulite facies rocks: decoupling from geochemistry above 850 °C?

Granulite facies rocks frequently show a large spread in their zircon ages, the interpretation of which raises questions: Has the isotopic system been disturbed? By what process(es) and conditions did the alteration occur? Can the dates be regarded as real ages, reflecting several growth episodes? Furthermore, under some circumstances of (ultra-)high-temperature metamorphism, decoupling of zircon U–Pb dates from their trace element geochemistry has been reported. Understanding these processes is crucial to help interpret such dates in the context of the P–T history. Our study presents evidence for decoupling in zircon from the highest grade metapelites (> 850 °C) taken along a continuous high-temperature metamorphic field gradient in the Ivrea Zone (NW Italy). These rocks represent a well-characterised segment of Permian lower continental crust with a protracted high-temperature history. Cathodoluminescence images reveal that zircons in the mid-amphibolite facies preserve mainly detrital cores with narrow overgrowths. In the upper amphibolite and granulite facies, preserved detrital cores decrease and metamorphic zircon increases in quantity. Across all samples we document a sequence of four rim generations based on textures. U–Pb dates, Th/U ratios and Ti-in-zircon concentrations show an essentially continuous evolution with increasing metamorphic grade, except in the samples from the granulite facies, which display significant scatter in age and chemistry. We associate the observed decoupling of zircon systematics in high-grade non-metamict zircon with disturbance processes related to differences in behaviour of non-formula elements (i.e. Pb, Th, U, Ti) at high-temperature conditions, notably differences in compatibility within the crystal structure

Developmental pathways to autism: a review of prospective studies of infants at risk

Autism Spectrum Disorders (ASDs) are neurodevelopmental disorders characterized by impairments in social interaction and communication, and the presence of restrictive and repetitive behaviors. Symptoms of ASD likely emerge from a complex interaction between pre-existing neurodevelopmental vulnerabilities and the child's environment, modified by compensatory skills and protective factors. Prospective studies of infants at high familial risk for ASD (who have an older sibling with a diagnosis) are beginning to characterize these developmental pathways to the emergence of clinical symptoms. Here, we review the range of behavioral and neurocognitive markers for later ASD that have been identified in high-risk infants in the first years of life. We discuss theoretical implications of emerging patterns, and identify key directions for future work, including potential resolutions to several methodological challenges for the field. Mapping how ASD unfolds from birth is critical to our understanding of the developmental mechanisms underlying this disorder. A more nuanced understanding of developmental pathways to ASD will help us not only to identify children who need early intervention, but also to improve the range of interventions available to them

"It was me on a good day" : exploring the smart drug use phenomenon in England

The non-medical use of prescription medication for the pursuit of increasing cognitive and intellectual capacities (defined neuroenhancement) has received growing attention from the scientific community and policymakers alike. To date, limited qualitative data exist exploring the nature of the phenomenon, especially as a potentially emerging trend among university students in England. Existing American literature suggests that students believe that neuroenhancement helps the individual to maximize his/her time, consenting a suitable balance between work and leisure. Students' motivation to experiment with neuroenhancement appears to be more in line with a need to regulate emotions surrounding study/work settings than to actually improve cognitive abilities beyond normal levels. This study aimed to qualitatively explore representations, motivations, beliefs, and consumption styles of a cohort of university student users residing in England. Through snowball sampling, 13 informants were contacted and interviewed regarding their experience with neuroenhancers. Narrations were analyzed and interpreted using qualitative analysis software and Grounded Theory methodology. Participants belonged to a broad variety of university courses and were predominantly habitual consumers of modafinil. Neuroenhancers were acquired either through friends or via the Internet. Motivations regarded the need to "catch up" and be on par with high achieving students. The entire cohort had previously experimented with other psychotropic substances. Synthetic compounds in particular were believed to be "gateway" drugs to using neuroenhancers. Experimentation with neuroenhancement can be seen as a self-governing strategy aimed at achieving continued focused productivity. Participants acknowledged sustainable benefits in neuroenhancement as it optimized work performance. The majority of the cohort also contemplated the possibility of using these drugs in the future once they entered the workforce. Neuroenhancing drug users expressed "situated morality," differentiating between using these substances for assessments (exams) or during revisions, finding only the former as an immoral conduct. In the present scenario, it appears that neuroenhancement is practiced by small numbers of students. Nonetheless, the instrumental views of psychotropic substances held by many young adults and the globalization of these practices make the normalization of neuroenhancement a plausible possibility of the future

Schooling for conflict transformation : a case study from Northern Uganda

Civil wars impede progress towards the Millennium Development Goals. As many conflicts erupt within a short time, it is important to know what may increase the chances of sustainable peace. Access to education is a factor but relatively little is known about the contribution of what students learn in school. This thesis aims to respond to a research gap by addressing the foll owing question: 'How can schooling contribute to conflict transformation?' Significant curricular approaches that may be used after civil war - peace education, human rights education and citizenship education - are assessed for their strengths and weaknesses. As no single approach is found to be sufficient for conflict transformation, a framework is proposed based on three fundamental concepts: (i) truth seeking; (ii) reconciliation; and (iii) inclusive citizenship. This framework is examined through a qualitative case study of curriculum in seven schools in a district in northern Uganda that is emerging from a twenty-year civil war. The curriculum of four primary schools, two secondary schools, one special school and one teacher training college was studied over a three-month period. A structure of knowledge, skills and values was used to research the framework at a detailed level. It is found that schools exhibit good socialization of reconciliation values and some development of problem-solving and communication skills. There is some understanding of human rights, but little knowledge of history, or of local, national and international political/legal systems. There is minimal development of discussion and critical thinking skills. It is argued that the framework can be used to investigate other schools and to inform the design of a curriculum that can contribute to conflict transformation, with the ultimate aim of reducing the risk of civil war re-eruption

Predicting breast cancer response to neoadjuvant treatment using multi-feature MRI: results from the I-SPY 2 TRIAL.

Dynamic contrast-enhanced (DCE) MRI provides both morphological and functional information regarding breast tumor response to neoadjuvant chemotherapy (NAC). The purpose of this retrospective study is to test if prediction models combining multiple MRI features outperform models with single features. Four features were quantitatively calculated in each MRI exam: functional tumor volume, longest diameter, sphericity, and contralateral background parenchymal enhancement. Logistic regression analysis was used to study the relationship between MRI variables and pathologic complete response (pCR). Predictive performance was estimated using the area under the receiver operating characteristic curve (AUC). The full cohort was stratified by hormone receptor (HR) and human epidermal growth factor receptor 2 (HER2) status (positive or negative). A total of 384 patients (median age: 49 y/o) were included. Results showed analysis with combined features achieved higher AUCs than analysis with any feature alone. AUCs estimated for the combined versus highest AUCs among single features were 0.81 (95% confidence interval [CI]: 0.76, 0.86) versus 0.79 (95% CI: 0.73, 0.85) in the full cohort, 0.83 (95% CI: 0.77, 0.92) versus 0.73 (95% CI: 0.61, 0.84) in HR-positive/HER2-negative, 0.88 (95% CI: 0.79, 0.97) versus 0.78 (95% CI: 0.63, 0.89) in HR-positive/HER2-positive, 0.83 (95% CI not available) versus 0.75 (95% CI: 0.46, 0.81) in HR-negative/HER2-positive, and 0.82 (95% CI: 0.74, 0.91) versus 0.75 (95% CI: 0.64, 0.83) in triple negatives. Multi-feature MRI analysis improved pCR prediction over analysis of any individual feature that we examined. Additionally, the improvements in prediction were more notable when analysis was conducted according to cancer subtype

The Concise Guide to PHARMACOLOGY 2023/24: Ion channels.

The Concise Guide to PHARMACOLOGY 2023/24 is the sixth in this series of biennial publications. The Concise Guide provides concise overviews, mostly in tabular format, of the key properties of approximately 1800 drug targets, and over 6000 interactions with about 3900 ligands. There is an emphasis on selective pharmacology (where available), plus links to the open access knowledgebase source of drug targets and their ligands (https://www.guidetopharmacology.org/), which provides more detailed views of target and ligand properties. Although the Concise Guide constitutes almost 500 pages, the material presented is substantially reduced compared to information and links presented on the website. It provides a permanent, citable, point-in-time record that will survive database updates. The full contents of this section can be found at http://onlinelibrary.wiley.com/doi/10.1111/bph.16178. Ion channels are one of the six major pharmacological targets into which the Guide is divided, with the others being: G protein-coupled receptors, nuclear hormone receptors, catalytic receptors, enzymes and transporters. These are presented with nomenclature guidance and summary information on the best available pharmacological tools, alongside key references and suggestions for further reading. The landscape format of the Concise Guide is designed to facilitate comparison of related targets from material contemporary to mid-2023, and supersedes data presented in the 2021/22, 2019/20, 2017/18, 2015/16 and 2013/14 Concise Guides and previous Guides to Receptors and Channels. It is produced in close conjunction with the Nomenclature and Standards Committee of the International Union of Basic and Clinical Pharmacology (NC-IUPHAR), therefore, providing official IUPHAR classification and nomenclature for human drug targets, where appropriate