Increase in hospitalisation-associated methadone intoxication in France following first COVID-19 lockdown.

OBJECTIVES: At the beginning of the COVID-19 pandemic, the French Addictovigilance Network drew attention to the need to facilitate access to methadone while ensuring its safe use, in order to avoid the occurrence of overdoses and deaths. The objectives of the study were to assess the impact of the lockdowns on the incidence of methadone-use-related hospitalisations (MUHs) and describe the characteristics of patients and hospitalisations. STUDY DESIGN: An interrupted time series using the unobserved components model was performed to predict the monthly incidence of MUHs in 2020 on the basis of previous years' data and compared with MUHs observed. Data were presented with prediction intervals (PI95%). METHODS: This retrospective study was conducted on patients hospitalised in France for methadone between 2014 and 2020, using the French national database hospital discharge database. Patients' characteristics and hospitalisations were described over four periods: before lockdown, first lockdown, after first lockdown, and second lockdown. RESULTS: Compared to the predictions, a higher incidence of MUH was found during the first lockdown, especially in March 2020 (66 cases vs. 51.3; PI95%: 34-65), and there was a large increase during the month following the end of the first lockdown (79 cases vs. 61; PI95%: 46-75). Coconsumptions (alcohol, cannabis, cocaine) were more frequent during the first lockdown, whereas patients aged over 30 years were more concerned thereafter. The second lockdown did not present any particularity. CONCLUSIONS: The first lockdown had a significant impact on the incidence of MUHs. These results confirm the data from the reinforced national monitoring during first lockdown published in 2020, where methadone was the primary substance involved in overdoses and deaths.

General hospital admissions in young and middle-aged people who use psychoactive substances: Impact of Covid-19 lockdowns.

BACKGROUNDS: The Covid-19 pandemic offered a unique opportunity to investigate trends in hospitalizations related to psychoactive substance intoxication, since the usual health burden of social use at parties and gatherings was likely to be decreased during lockdowns and curfew periods. Since young adults are the main users of psychoactive substances for experimental and recreational purposes, this study identified and compared hospitalization trends in young adults and adults over 30 years old. METHODS: This national cohort study was conducted using the French hospital discharge database. An interrupted time-series analysis for the period between 2014 and 2020 was performed in two groups: young (age 18-29) and other adults (30+) to ascertain the trends in the monthly incidence of hospitalization related to psychoactive substance intoxication (opiates, cocaine, benzodiazepines, psychostimulants, alcohol and cannabis). Hospitalization characteristics during the first and second lockdown and the period between them were compared to the reference period (from 01/01/2014 to 29/02/2020). RESULTS: Among 1,358,007 stays associated with psychoactive substance intoxication, 215,430 concerned young adults. Compared with adults 30+, hospitalization trends in young adults showed a greater decrease in the number of stays during lockdown, with a maximum decrease of -39% during the first lockdown (1,566 vs. 2,576; CI95%: 2,285-2,868) versus -20% (10,212 vs. 12,894; CI95%: 12,001-13,787) in the second lockdown. Presentations for alcohol intoxication decreased throughout the pandemic, particularly during the second lockdown, while admissions for benzodiazepine intoxication increased during both lockdowns. Admissions for cannabis intoxication increased throughout the entire period. CONCLUSIONS: Lockdowns were associated with fewer hospitalizations related to psychoactive substance intoxication in both age groups, especially among young adults, which might reflect a decrease in social use. Recreational use might therefore be an important target for prevention and risk minimization.

Suitability of infrared spectroscopy for drug checking in harm reduction centres.

Drug checking is a service for people who use drugs that includes product analysis and an individual interview including results feedback and harm reduction counselling. It uses different analytical methods but few studies demonstrate their value in current practice. The main objective of this work is to compare the analytical performance of IR spectroscopy to laboratory reference method in the context of drug checking in a harm reduction centre. The secondary objectives are to carry out a description of the people who use drugs requesting a product analysis, and to compare the assumed compositions of products purchased with their real compositions. During 2018, all requests for drug testing analysis were included for on-site analysis by IR spectrometry in a harm reduction center and verified by the reference method (UPLC-HRMS) at Bordeaux University Hospital Center. Socioeconomic and product data were also collected. One hundred and thirty-six samples were collected. The results obtained with IR and UPLC-HRMS were compared. IR spectrometry results did not match with reference method in 8 % (n=11) of cases, corresponding to blotters, cannabis and some psychoactive substances present in mixture or in small quantities. Among the products collected, only 5.1 % (n=7) did not correspond to the declared product, either alone or with adulterants. The IR spectrometer allows a simple and rapid detection of at least one molecule, most often the one of interest. However, it is limited to powder and tablet type matrices and is not suitable for blotters, cannabis, mixed or low content substances for which high resolution mass spectrometry remains the reference method.

Acute Methiopropamine Intoxication After "Synthacaine" Consumption.

Use of methiopropamine (MPA), a synthetic metamfetamine analog, has been detected since 2011 in Europe, but there is limited information on its acute toxicity. A 30-year-old man was admitted to the emergency department in a confused state, with paranoid delusion, auditory and visual hallucinatory experiences, and incoherent speech following the use of "synthacaine" (a slang term derived from "synthetic" and "cocaine"). Toxicological screening for pharmaceuticals and drugs of abuse by liquid chromatography-diode-array detector, gas chromatography-mass spectrometry and liquid chromatography-tandem mass spectrometry (LC-MS-MS) detected MPA, which was subsequently quantified by a specific LC-MS-MS method. Of note, 13 h after presentation to the emergency department, the plasma concentration of MPA was 14 ng/mL. This case report confirms the toxicity of MPA and the need for toxicological analysis to confirm the substance actually ingested by users of new psychoactive substances.

Identification of abuse and dependence cases through a hospital database.

UNLABELLED: Computerized hospital databases are used for clinical and economic research. In France, the hospital administrative database, Programme de médicalisation des systèmes d'information (PMSI), could be an interesting means for identifying cases of abuse and dependence in hospitals. PURPOSE: To assess the capability of PMSI to identify cases of abuse and dependence (medicines or illicit drugs; tobacco and alcohol not included). METHODS: Cross-sectional study, from October 1 to December 31, 2008, in teaching hospitals of Bordeaux. All hospitalizations with an ICD-10 code related to possible abuse or dependence were selected. Cases were validated by a committee composed of three pharmacologists using discharge summaries. RESULTS: Among the 34 816 patients registered in the PMSI during the study period, a total of 227 patients were pre-selected as potential cases; 21 patients, hospitalized for abuse or dependence, or complications of which, were included in the analysis. Mean age was 35 years. Substances implicated were buprenorphine (n = 8), benzodiazepines (n = 7), cannabis (n = 6), cocaine (n = 4), heroin (n = 3), amphetamine, ecstasy, morphine, codeine, and tramadol (n = 1, respectively); there was polydrug use in six cases. CONCLUSIONS: The PMSI database can be useful to identify certain cases of abuse and dependence. This pilot study has been conducted at a local level; as the PMSI is available in all hospital settings in France, further analysis could be done at the regional and national levels. Such data could be a valuable indicator to analyze trends and assess the medical consequences of substance abuse.

Inhibition of the binding of dexamethasone to mammary cytoplasmic glucocorticoid receptor by phenylglyoxal.

We have studied the effects of phenylglyoxal and other related arginine-specific reagents on the mammary cytoplasmic glucocorticoid receptor. Our studies show that phenylglyoxal can inhibit the binding of [3H]dexamethasone to the steroid-free receptor and also displace the bound [3H]dexamethasone from the steroid-receptor complex. The kinetics of the binding reaction reveals that the inhibition of phenylglyoxal may be due to its ability to interact with the steroid binding site of the receptor. Similar data are also obtained with other arginine-modifying agents such as 1,2-cyclohexanedione. Thus, these studies suggest that arginine residues may be involved in the binding of glucocorticoids to mammary cytoplasmic glucocorticoid receptor.