The Pharmacological Management of Ketamine Use Disorder: A Systematic Review

OBJECTIVES: There has been limited evidence synthesis examining treatment of ketamine use disorder. We aimed to conduct a systematic review to assess the efficacy and tolerability of pharmacological interventions in the management of ketamine use disorder. METHODS: We searched MEDLINE, EMBASE, PsychINFO, and CENTRAL (Cochrane Central Register of Controlled Trials) from database inception to November 14, 2023, for studies of any design that reported on any pharmacological intervention in the management of ketamine use disorder. We extracted any reported measure of efficacy or tolerability and assessed outcome quality using the GRADE (Grading of Recommendations Assessment, Development, and Evaluation) framework. We planned to combine outcomes using random-effects meta-analysis, where this was not possible results were reported narratively. RESULTS: Twelve studies met the inclusion criteria reporting on 368 participants. These comprised 1 controlled trial, 2 retrospective case series, and 9 case reports. Two studies reported on ketamine intoxication, 6 on withdrawal, and 4 on craving/relapse prevention. All studies reported only descriptive outcomes, and all evidence was of very low quality. Benzodiazepine regimens and haloperidol were reported to have potential utility in intoxication and withdrawal, whereas naltrexone, lamotrigine, and a combination of paliperidone palmitate and bupropion were reported to have potential utility in craving/relapse prevention. CONCLUSIONS: There is a paucity of research into pharmacological management of ketamine use disorder. The limited very low-quality evidence suggests benzodiazepine regimens may be most salient for future exploration in management of ketamine intoxication and withdrawal, whereas case reports suggest naltrexone, lamotrigine, and paliperidone palmitate plus bupropion may potentially merit further investigation with regard to craving/relapse prevention.</p

L’organisation du temps libre : les foyers du soldat en Italie

L’Italie entre en guerre le 24 mai 1915, presque dix mois après les autres puissances. Auparavant, ni l’armée ni l’État n’étudient un éventuel plan d’action pour le temps libre des combattants. Si les autorités civiles et militaires étaient pleinement convaincues que la guerre serait de courte durée, la principale raison de cette carence trouve son origine dans la traditionnelle passivité des pouvoirs publics en matière d’assistance aux classes défavorisées, y compris concernant leur temps li..

The Evolution and Treatment of Korsakoff's Syndrome

Abstract Wernicke’s Encephalopathy is an acute neuro-psychiatric condition caused by an insufficient supply of thiamine (Vitamin B1) to the brain. If undiagnosed or inadequately treated, it is likely to proceed to Korsakoff’s Syndrome. Wernicke’s Encephalopathy can result from dietary deficiency alone and this form is usually successfully treated, with little chance of Korsakoff’s Syndrome supervening. On the other hand, thiamine deficiency associated with alcohol misuse/dependence may require up to 1 gram of thiamine IV in the first 24 hours to be treated successfully. The reasons for this difference in treatment will be discussed. Thiamine diphosphate acts as a co-factor for a number of thiamine-dependent enzymes. Thiamine deficiency leads to a reduction in the activity of these enzymes, and this leads to alterations in mitochondrial activity, impairment of oxidative metabolism, decreased energy status and eventually selective neuronal death. The damage caused by the combination of thiamine deficiency and alcohol metabolism probably interferes with adequate thiamine transport at a number of sites in the body, including the blood–brain barrier, as well as causing damage to the apoenzymes which then require higher concentrations of thiamine to work normally. The accumulated damage is likely to render the use of oral thiamine therapeutically inadequate since the body is unable to produce high enough concentrations of thiamine in the blood to traverse the blood–brain barrier. Some individuals are probably genetically predisposed to develop Wernicke’s. Long before individuals with alcohol misuse or dependence develop Wernicke’s Encephalopathy the neurons and other cells of the body are functioning sub-optimally because of the inadequate supply of thiamine and the neurotoxic effect of alcohol. This relative deficiency initiates a series of pathological changes which accumulate and further interfere with the supply of thiamine and its utilisation at a time when the requirements are increased. The best treatment for Korsakoff’s Syndrome is timely recognition of Wernicke’s Encephalopathy and appropriate intervention and prevention.</jats:p

Bergamot (Citrus bergamia Risso) fruit extracts and identified components alter expression of interleukin 8 gene in cystic fibrosis bronchial epithelial cell lines

<p>Abstract</p> <p>Background</p> <p>Cystic fibrosis (CF) airway pathology is a fatal, autosomal, recessive genetic disease characterized by extensive lung inflammation. After induction by TNF-α, elevated concentrations of several pro-inflammatory cytokines (i.e. IL-6, IL-1β) and chemokines (i.e. IL-8) are released from airway epithelial cells. In order to reduce the excessive inflammatory response in the airways of CF patients, new therapies have been developed and in this respect, medicinal plant extracts have been studied. In this article we have investigated the possible use of bergamot extracts (<it>Citrus bergamia </it>Risso) and their identified components to alter the expression of IL-8 associated with the cystic fibrosis airway pathology.</p> <p>Methods</p> <p>The extracts were chemically characterized by ¹H-NMR (nuclear magnetic resonance), GC-FID (gas chromatography-flame ionization detector), GC-MS (gas chromatography-mass spectrometry) and HPLC (high pressure liquid chromatography). Both bergamot extracts and main detected chemical constituents were assayed for their biological activity measuring (a) cytokines and chemokines in culture supernatants released from cystic fibrosis IB3-1 cells treated with TNF-α by Bio-Plex cytokine assay; (b) accumulation of IL-8 mRNA by real-time PCR.</p> <p>Results</p> <p>The extracts obtained from bergamot (<it>Citrus bergamia </it>Risso) epicarps contain components displaying an inhibitory activity on IL-8. Particularly, the most active molecules were bergapten and citropten. These effects have been confirmed by analyzing mRNA levels and protein release in the CF cellular models IB3-1 and CuFi-1 induced with TNF-α or exposed to heat-inactivated <it>Pseudomonas aeruginosa</it>.</p> <p>Conclusions</p> <p>These obtained results clearly indicate that bergapten and citropten are strong inhibitors of IL-8 expression and could be proposed for further studies to verify possible anti-inflammatory properties to reduce lung inflammation in CF patients.</p

A versatile clearing agent for multi-modal brain imaging

Extensive mapping of neuronal connections in the central nervous system requires high-throughput um-scale imaging of large volumes. In recent years, different approaches have been developed to overcome the limitations due to tissue light scattering. These methods are generally developed to improve the performance of a specific imaging modality, thus limiting comprehensive neuroanatomical exploration by multimodal optical techniques. Here, we introduce a versatile brain clearing agent (2,2'-thiodiethanol; TDE) suitable for various applications and imaging techniques. TDE is cost-efficient, water-soluble and low-viscous and, more importantly, it preserves fluorescence, is compatible with immunostaining and does not cause deformations at sub-cellular level. We demonstrate the effectiveness of this method in different applications: in fixed samples by imaging a whole mouse hippocampus with serial two-photon tomography; in combination with CLARITY by reconstructing an entire mouse brain with light sheet microscopy and in translational research by imaging immunostained human dysplastic brain tissue.Comment: in Scientific Reports 201

Perioperative Use of IgM-Enriched Immunoglobulins in Liver Transplantation Recipients at High Risk for Infections: A Preliminary Study

: Background: Infections frequently occur after orthotopic liver transplantation (OLT) and are associated with increased mortality. In 2018, we introduced perioperative administration of intravenous immunoglobulin enriched in IgM as an optional therapy in recipients at a high risk of infection. This preliminary study evaluated whether this preparation reduced infections in the early post-transplantation period. Methods: Adult patients with a high risk of postoperative infections who underwent OLT between January 2014 and December 2021 in our center were included in the study. The primary outcome was the occurrence of new postoperative bacterial and fungal infections within the first 30 days after OLT. Results: Ninety recipients at a high risk of postoperative infections who underwent OLT were included, of whom 51 (57%) received IgM preparation. Patients treated and not treated with IgM were similar in terms of demographics, model of end-stage liver disease score, and risk factors for postoperative infections. The occurrence of new infections was lower (absolute risk reduction (ARR) 21.2%; p = 0.038) in patients who received IgM than in those who did not. Multivariate analysis adjusted for confounders (OR 0.348; p = 0.033) and propensity score-based matching analysis (ARR 21.2%, p = 0.067) confirmed an association between IgM preparation and lower occurrence of postoperative infections. The 90-day mortality rate was lower (ARR 13.4%, p = 0.018) in patients who received IgM preparation. Conclusions: In OLT recipients at high risk for infections, perioperative administration of an IgM-enriched preparation seems to reduce the development of new infections within the first 30 days after OLT

A follow up study on the efficacy of metadoxine in the treatment of alcohol dependence

BACKGROUND: We carried out a three months follow-up study on the efficacy of metadoxine in a cohort of alcoholics admitted to the Alcohol misuse Long-term Treatment (ALT) Unit – University of Pisa (Italy). We analyzed the clinical data, psychometric tests and blood tests of 160 alcoholics on admission and after 3 months of treatment. We compared 58 pts treated with metadoxine (MET) with 102 pts who did not receive (NULL) any drug as an adjunct to the psycho-educational interventions provided by the ALT Unit. RESULTS: At follow-up, the patients in treatment with metadoxine showed a significant improvement in the rate of complete abstinence (44.8% vs. 21.6%; chi square: 8.45, df = 1, p < 0.0037). Furthermore, the number of drop-outs at three months of treatment was also significantly lower in the MET than in the NULL group (17% vs. 57%; chi square of 23.22, df = 1, p < 0.001). CONCLUSION: Our findings support the use of metadoxine in the management of alcohol dependence. However, randomized clinical trials are necessary to confirm and replicate them. This study raises the importance of identifying new pharmacological compounds effective on the outcome of alcoholism in order to help patients to best adhere to treatment programs and to prevent the development of mental and physical complications due to chronic and heavy use of alcohol