Gradual enhancement of corticomotor excitability during cortico-cortical paired associative stimulation

Cortico-cortical paired associative stimulation (ccPAS) is an effective transcranial magnetic stimulation (TMS) method for inducing associative plasticity between interconnected brain areas in humans. Prior ccPAS studies have focused on protocol’s aftereffects. Here, we investigated physiological changes induced “online” during ccPAS administration. We tested 109 participants receiving ccPAS over left ventral premotor cortex (PMv) and primary motor cortex (M1) using a standard procedure (90 paired-pulses with 8-ms interstimulus interval, repeated at 0.1 Hz frequency). On each paired-pulse, we recorded a motor-evoked potential (MEP) to continuously trace the emergence of corticomotor changes. Participant receiving forward-ccPAS (on each pair, a first TMS pulse was administered over PMv, second over M1, i.e., PMv-to-M1) showed a gradual and linear increase in MEP size that did not reach a plateau at the end of the protocol and was greater in participants with low motor threshold. Participants receiving reverse-ccPAS (i.e., M1-to-PMv) showed a trend toward inhibition. Our study highlights the facilitatory and inhibitory modulations that occur during ccPAS administration and suggest that online MEP monitoring could provide insights into the malleability of the motor system and protocol’s effectiveness. Our findings open interesting prospects about ccPAS potential optimization in experimental and clinical settings

intensive nutritional counselling and support and clinical outcomes in hemodialysis patients

Protein-energy wasting is frequently found in haemodialysis (HD) patients. Anorexia and hypophagia contribute to malnutrition, increased morbidity and mortality, but the clinical impact of correcting hypophagia remains uncertain. We evaluated whether correction of hypophagia influences morbidity and mortality in anorexic HD patients. Thirty-four HD patients were enrolled in a 2-year follow-up programme including regular nutritional assessment. Patients not meeting nutritional requirements during the follow-up, received nutritional counselling, consisting of advice, individually tailored diet and, in case of failure of dietary intervention, artificial nutrition. Biochemical, anthropometric, body composition parameters, morbidity and mortality were recorded in all patients at 12 and 24 months. At baseline, 14 patients (41%) were anorexic, and 20 patients (59%) non-anorexic. Anorexic patients were hypophagic and presented with reduced fat-free mass. After 12 and 24 months, cholesterol, albumin, lymphocyte count and BMI did not differ among groups, while FFM (%) in supplemented anorexic patients significantly improved, being not different any more vs non-anorexic (65.8±4.4 vs 65.4±8.9, respectively; p=n.s.; 65.8±4.4 vs 66.7±10.78, respectively; p=n.s.). Morbidity and mortality were not different among the two groups. In conclusion, in HD patients, nutritional counselling and nutritional support positively affect nutritional status in hypophagic patients and make the risk of morbidity and mortality in anorexic patients comparable to non-anorexic

Brexpiprazole as a new approach of treatment in somatization disorder

© 2022 Published by Elsevier Ltd on behalf of International Society for the Study of Emerging Drugs. This is an open access article under the CC-BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/)Introduction: Somatic symptom disorder (SSD) is a mental disorder that involves one or more physical symptoms (e.g. palpitations, dizziness, diarrhoea, limb weakness, pain, and pseudo neurological symptoms) accompanied by one or more thoughts, feelings, and/or behaviours related to the somatic symptom(s) resulting in significant distress and/or dysfunction lasting for more than 6 months. At now the SSD can be refractory to psychiatric intervention including antidepressants, antiepileptics, and antipsychotics as well as the effectiveness of many of these treatments is limited. The objective of this study was to report the effectiveness of a third-generation antipsychotic drug brexpiprazole for treatment of a case of SSD together with the serotonin selective reuptake inhibitor (SSRI) fluvoxamine. Methods: A single case study of a 59-year-old female with SSD was here performed. Findings: After 4 weeks of treatment brexpiprazole, together with lamotrigine and fluvoxamine, was here effective in decreasing both depressive and anxiety symptoms, normalising previous unusual thought contents and of related behaviours. The patient reported an overall good response and started to function again in important domains of life. No adverse events occurred. Conclusion: To our knowledge, this is the first case showing Brexpiprazole effective for the treatment of a case of SSD as add-on to other drugs.Peer reviewedFinal Published versio

Fatigue in Patients on Chronic Hemodialysis: The Role of Indoleamine 2,3-Dioxygenase (IDO) Activity, Interleukin-6, and Muscularity

Fatigue is a frequent symptom in hemodialysis (HD), and the indolamine-2,3-dioxygenase (IDO) metabolic trap has been hypothesized in the pathogenesis of fatigue. The association between IDO activity according to fatigue and its relationship with muscle mass and function in HD patients was verified. Chronic HD patients were considered, and fatigue was assessed. The plasma kynurenines and tryptophan ratio (Kyn/Trp), as surrogate of IDO activity, and interleukin (IL)-6 were measured. Muscularity was assessed by BIA and muscle strength by hand-grip dynamometer. 50 HD patients were enrolled, and fatigue was present in 24% of the cohort. Patients with fatigue showed higher Kyn/Trp (p = 0.005), were older (p = 0.007), and IL-6 levels resulted higher than in non-fatigue patients (p < 0.001). HD patients with fatigue showed lower intracellular water (surrogate of muscle mass) (p < 0.001), as well as lower hand grip strength (p = 0.02). The Kyn/Trp ratio positively correlated with IL-6 and ECW/ICW (p = 0.004 and p = 0.014). By logistic regression analysis, higher ICW/h(2) was associated with lower odds of fatigue (OR, 0.10; 95% CI, 0.01 to 0.73). In conclusion, our cohort fatigue was associated with a higher Kyn/Trp ratio, indicating a modulation of IDO activity. The Kyn/Trp ratio correlated with IL-6, suggesting a potential role of IDO and inflammation in inducing fatigue and changes in muscularity

The benzydamine experience: a systematic review of benzydamine abuse

Submitted 25 August 2020. Revised 14 December 2020. Accepted 19 December 2020. Abstract published online 13 January 2021. Full Article 19 November 2021.Background: Both prescription and over-the-counter (OTC) drugs recently emerged among novel psychoactive substances (NPS) being reported as ingested for recreational purposes. Among them, benzydamine (BZY), normally prescribed as an OTC anti-inflammatory drug, is reportedly being diverted and recreationally used. Objective: The aim of this study was to investigate how the misuse of BZY has been reported, illustrating its psychotropic molecular mechanism, and studying its psychopathological effects. Methods: We firstly conducted a systematic review of the literature concerning the abuse of BZY and its effects. For data gathering purposes, both PRISMA and PROSPERO guidelines were followed. All research methods were approved by PROSPERO (identification code CRD42020187266). Second, we analysed BZY-related data from the European Monitoring Agency (EMA) Adverse Drug Reactions (ADRs) database recorded during 2005-2020 regarding its abuse. Results: Eleven articles, published during 1997-2019, were included in our systematic review, including five case reports, four surveys, and two retrospective case series analyses. While nine articles dealt with a recreational use of BZY, two described an oral overdose of the drug. When specified, dosages of BZY consumed ranged from 500 to 1500mg. The EMA dataset contained three cases of BZY abuse. Conclusion: Results from the systematic review showed BZY might be diverted for typical hallucinogenic properties which occur at high dosages. Healthcare professionals should be warned about a possible misuse/abuse of a commonly prescribed anti-inflammatory drug and be vigilant when prescribing it. Physicians working in emergency units should know that psychotic symptoms may be related to BZY abuse.Peer reviewe

Recreational Drug Misuse and Its Potential Contribution to Male Fertility Levels’ Decline: A Narrative Review

© 2022 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 (https://creativecommons.org/licenses/by/4.0/)Recreational drug intake may be associated with a range of medical untoward consequences, including male infertility. However, as the related evidence is still limited, the main outcome of this review is to provide a better understanding of the existence of any association between recreational drug misuse and male fertility levels’ decline. Whilst searching the MEDLINE/PubMed, a comprehensive overview of the literature regarding male infertility and substances of abuse (e.g., phytocannabinoids, opiates/opioids, stimulants, ‘herbal highs’, psychedelics, and ‘novel psychoactive substances) was here undertaken. Due to the paucity of robust, high-quality, empirical, human studies, a narrative strategy was here preferred over a systematic approach. Relevant data are qualitatively analyzed and presented in a table. Although most available evidence is in support of a detrimental role of cannabis on human spermatogenesis, a few remaining studies failed to document any effect of this drug on seminal quality, and it is not clear to which extent this drug impacts fertility rates/time to pregnancy. The current understanding of the impact of opiate-, cocaine- and amphetamine/stimulant-misuse on human reproduction is widely unknown, and most studies dealing with this matter represent only an extrapolation of data derived from specific clinical circumstances. Although the message of ‘no smoking, no alcohol and no street drugs’ should always be offered as good health advice to all patients seeking medical help for fertility issues, robust scientific clinical evidence in support of a direct detrimental impact of recreational drugs on spermatogenesis is scant to date.Peer reviewe

New Psychoactive Substances and Suicidality: A Systematic Review of the Current Literature

Submitted 23 April 2021. Minor revisions requested 31 May 2021. Revisions submitted 3 June 2021. Accepted 3 June 2021. Epub 6 June 2021.Background and Objectives: Over the past twenty years a large number of New Psychoactive Substances (NPS) has entered and modified the recreational drug scene. Their intake has been associated with health-related risks, and especially so for vulnerable populations such as people with severe mental illness, who might be at higher risk of suicidality or self- injurious behaviour. This paper aims at providing an overview of NPS abuse and effects on mental health and suicidality issues, performing a literature review of the current related knowledge, thereby identifying substances that more than others are linked to suicidal behaviours. Materials and Methods: A comprehensive and updated overview of the literature regarding suicidality and NPS categories has been provided. An electronic search was performed, including all papers published up to March 2021, using the following keywords "NPS" OR "new psychoactive substances" OR "novel psychoactive substances" OR "synthetic cannabinoids" OR "phenethylamines" OR "synthetic cathinones" OR “tryptamines” OR “piperazines” OR “new synthetic opioids” OR “designer benzodiazepines”) AND ("suicide" OR "suicidality") NOT review NOT animal on the PubMed, Cochrane Library, and Web of Science online databases. Results: Suicidality and self-injurious behaviour appear to be frequently associated with some NPS such as cathinones, synthetic cannabinoids, and new synthetic opioids. Results are organised according to substances recorded. Conclusion: The growing use of NPS has become a significant clinical issue, posing increasing concern and challenges for clinicians working in both mental health and emergency departments. Thus, considering the associations between NPS and suicidality or self-injurious behaviours, areas where suicide-prevention efforts and strategies might be focused are the early detection, monitoring and restriction of NPS.Peer reviewe

Focus on Over-the-Counter Drugs' Misuse: A Systematic Review on Antihistamines, Cough Medicines, and Decongestants

© 2021 Schifano, Chiappini, Miuli, Mosca, Santovito, Corkery, Guirguis, Pettorruso, Di Giannantonio and Martinotti. 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/Background: Over the past 20 years or so the drug misuse scenario has seen the emergence of both prescription-only and over-the-counter (OTC) medications being reported as ingested for recreational purposes. OTC drugs such as antihistamines, cough/cold medications and decongestants, are reportedly the most popular in being diverted and misused. Objective: Whilst the current related knowledge is limited, the aim was here to examine the published clinical data on OTC misuse, focusing on: antihistamines (e.g., diphenhydramine, promethazine, chlorpheniramine, and dimenhydrinate); dextromethorphan (DXM)- and codeine-based cough medicines; and the nasal decongestant pseudoephedrine. Methods: A systematic literature review was carried out with the help of Scopus; Web of Science databases; and the related grey literature. For data gathering purposes, both the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) and PROSPERO guidelines were followed (PROSPERO identification code CRD42020209261). Results: After completion of the selection, eligibility and screening phases, some 92 articles were here taken into consideration; case reports, surveys, and retrospective case series analyses were included. Findings were organised according to the specific OTC recorded. Most articles focussed here on DXM (n=54) and diphenhydramine (n=12). When specified, dosages, route(s) of administration, toxicity symptoms (including both physical and psychiatric ones), and outcomes were here reported. Conclusion: Results from the systematic review showed that the OTC misusing issues are both widespread worldwide and popular; vulnerable categories include adolescents and young adults, although real prevalence figures remain unknown, due to a lack of appropriate monitoring systems. Considering the potential, and at times serious, adverse effects associated with OTC misusing issues, healthcare professionals should be vigilant and ad hoc preventative actions should be designed and implemented.Peer reviewe

Therapeutic Potentials of Ketamine and Esketamine in Obsessive–Compulsive Disorder (OCD), Substance Use Disorders (SUD) and Eating Disorders (ED): A Review of the Current Literature

The obsessive–compulsive spectrum refers to disorders drawn from several diagnostic categories that share core features related to obsessive–compulsive disorder (OCD), such as obsessive thoughts, compulsive behaviors and anxiety. Disorders that include these features can be grouped according to the focus of the symptoms, e.g., bodily preoccupation (i.e., eating disorders, ED) or impulse control (i.e., substance use disorders, SUD), and they exhibit intriguing similarities in phenomenology, etiology, pathophysiology, patient characteristics and clinical outcomes. The non-competitive N-methyl-D-aspartate receptor (NMDAr) antagonist ketamine has been indicated to produce remarkable results in patients with treatment-resistant depression, post-traumatic stress disorder and OCD in dozens of small studies accrued over the past decade, and it appears to be promising in the treatment of SUD and ED. However, despite many small studies, solid evidence for the benefits of its use in the treatment of OCD spectrum and addiction is still lacking. Thus, the aim of this perspective article is to examine the potential for ketamine and esketamine in treating OCD, ED and SUD, which all involve recurring and intrusive thoughts and generate associated compulsive behavior. A comprehensive and updated overview of the literature regarding the pharmacological mechanisms of action of both ketamine and esketamine, as well as their therapeutic advantages over current treatments, are provided in this paper. An electronic search was performed, including all papers published up to April 2021, using the following keywords (“ketamine” or “esketamine”) AND (“obsessive” OR “compulsive” OR “OCD” OR “SUD” OR “substance use disorder” OR “addiction” OR “craving” OR “eating” OR “anorexia”) NOT review NOT animal NOT “in vitro”, on the PubMed, Cochrane Library and Web of Science online databases. The review was conducted in accordance with preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines. The use and efficacy of ketamine in SUD, ED and OCD is supported by glutamatergic neurotransmission dysregulation, which plays an important role in these conditions. Ketamine’s use is increasing, and preliminary data are optimistic. Further studies are needed in order to better clarify the many unknowns related to the use of both ketamine and esketamine in SUD, ED and OCD, and to understand their long-term effectiveness.Peer reviewedFinal Published versio

Knowledge and use of over-the-counter drugs in Italy: a survey-based study in the general population

© 2023 Bentham Science Publishers. This is the accepted manuscript version of an article which has been published in final form at http://dx.doi.org/10.2174/1570159X20666220714104231Background: During the past decade, the misuse of over-the-counter (OTC) medicines has become a global public health concern, especially among young people. In this study, we aimed to explore the OTC consumption and related misuse in Italy and identify the demographic characteristics of people/individuals involved in this phenomenon, understanding eventual risk factors. Methods: The study consisted of an anonymous online survey distributed by direct contact and via the Internet between June-November 2021 to the general population living in Italy. Descriptive sta-tistics were reported, and binary regression analyses were performed to identify risk factors for life-time misuse of OTC. The University of Hertfordshire approved the study (aLMS/SF/UH/02951). Results: The final sample size was composed of 717 respondents. The sample was mainly repre-sented by female (69.3%) students (39.9%) in the 20-25 years age group (30.0%). Based on the survey responses, study participants were divided into two groups according to the presence/absence of OTC abuse/misuse (127 versus 590), which were compared for possible predictors of OTC diver-sion. Multivariate regression showed that OTC abuse/misuse was associated with the knowledge of the effects of OTC [odds ratio/OR = 2.711, 95%Confidence Interval/CI 1.794-4.097, p <0.001]. On the contrary, the educational level appeared to be a protective factor [OR = 0.695, 95%CI 0.58–0.94, p = 0.016]. Conclusion: Although, according to our data, the phenomenon of OTC abuse appeared to be lim-ited, increasing attention is needed because of possible underestimation and high-risk outcomes. Preventive strategies, including simplified access to information, may play a key role in limiting OTC misuse.Peer reviewe