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.

Risk of discontinuation of antipsychotic long-acting injections vs. oral antipsychotics in real-life prescribing practice: a community-based study.

OBJECTIVE: To compare the risk of discontinuation of ambulatory antipsychotic treatment in persons treated with antipsychotic long-acting injections (LAIs) or by oral antipsychotics (OAPs). METHODS: The study was performed in a representative sample of persons newly treated with OAPs (n = 6904) affiliated to the French Insurance Healthcare system. The risk of all-cause discontinuation was compared in patients prescribed OAPs (n = 246) vs. matched patients prescribed LAIs (n = 246) using multivariate survival analyses. Confounding by indication was minimized by matching on type of antipsychotic drug and by the high-dimensional propensity score method. RESULTS: Discontinuation was more frequent with OAPs (69%) compared to LAIs (57%) [adjusted relative risk (aRR) = 1.6, 95% CI 1.23-2.07]. Risk of discontinuation was higher for first-generation (FGA) OAPs vs. FGA LAIs (aRR = 1.94, 95% CI 1.22-3.08) as well as for second-generation (SGA) OAPs vs. SGA LAIs (aRR = 1.58, 95% CI 1.15-2.17). Over the 6-month period after discontinuation of LAIs, a new antipsychotic drug was dispensed in 58% of patients, the most frequent pattern being dispensing of the same LAI as that prescribed before discontinuation. CONCLUSIONS: Although less frequent than with OAPs, the rate of ambulatory treatment discontinuation was high with LAIs. Prescription of LAIs should be associated with intervention strategies aimed at promoting medication adherence.

Use of the recommended drug combination for secondary prevention after a first occurrence of acute coronary syndrome in France.

PURPOSE: The recommended pharmacotherapy for secondary prevention of acute coronary syndrome (ACS) is long-term treatment with a combination of four therapeutic classes: beta-blockers, antiplatelet agents (including aspirin), statins or other lipid-lowering agents, and angiotensin-converting enzyme inhibitors or angiotensin receptor blockers. The aim of this study was to describe use and persistence of the recommended drug combination after the first occurrence of ACS in France. METHODS: This was a database cohort study of patients with first registration for ACS between 2004 and 2007 in a representative sample of the French healthcare insurance database (Echantillon Généraliste de Bénéficiaires, EGB). The drugs of interest were those recommended. Persistence was assessed for patients dispensed three or all four drug classes within 2 months following ACS. Discontinuation was defined by a gap of more than 6 weeks between two dispensations. The follow-up period was 24 months after ACS occurrence. RESULTS: Of 2,057 patients with incident ACS, 872 (42.4 %) had at least one dispensation of each of the four recommended drug classes, and 684 (33.3 %) had three of the four classes. Persistence to treatment at 24 months was 57.4 % (95 % CI [54.0-60.6]) for patients with four classes, and 55.5 % (95 % CI [51.6-59.1]) with three classes. Discontinuation of initial combination was higher in patients aged ≥ 65 years at ACS occurrence, those with associated ongoing chronic disease, and in those who did not suffer myocardial infarction. CONCLUSIONS: Post-ACS secondary prevention in France is not optimal, especially in patients who did not have myocardial infarction.

Dosimetric feasibility study ("proof of concept") of refractory ventricular tachycardia radioablation using proton minibeams.

PURPOSE: Preclinical data demonstrated that the use of proton minibeam radiotherapy reduces the risk of toxicity in healthy tissue. Ventricular tachycardia radioablation is an area under clinical investigation in proton beam therapy. We sought to simulate a ventricular tachycardia radioablation with proton minibeams and to demonstrate that it was possible to obtain a homogeneous coverage of an arrhythmogenic cardiac zone with this technique. MATERIAL AND METHODS: An arrhythmogenic target volume was defined on the simulation CT scan of a patient, localized in the lateral wall of the left ventricle. A dose of 25Gy was planned to be delivered by proton minibeam radiotherapy, simulated using a Monte Carlo code (TOPAS v.3.7) with a collimator of 19 0.4 mm-wide slits spaced 3mm apart. The main objective of the study was to obtain a plan ensuring at least 93% of the prescription dose in 93% of the planning target volume without exceeding 110% of the prescribed dose in the planning target volume. RESULTS: The average dose in the planning treatment volume in proton minibeam radiotherapy was 25.12Gy. The percentage of the planning target volume receiving 93% (V93%), 110% (V110%), and 95% (V95%) of the prescribed dose was 94.25%, 0%, and 92.6% respectively. The lateral penumbra was 6.6mm. The mean value of the peak-to-valley-dose ratio in the planning target volume was 1.06. The mean heart dose was 2.54Gy versus 5.95Gy with stereotactic photon beam irradiation. CONCLUSION: This proof-of-concept study shows that proton minibeam radiotherapy can achieve a homogeneous coverage of an arrhythmogenic cardiac zone, reducing the dose at the normal tissues. This technique, ensuring could theoretically reduce the risk of late pulmonary and breast fibrosis, as well as cardiac toxicity as seen in previous biological studies in proton minibeam radiotherapy.

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.

Effects of iloprost in patients with critical limb ischemia: Results of a cohort study from the COPART registry.

BACKGROUND: Iloprost has been proposed as an alternative to amputation in Critical Limb Ischemia (CLI) patients when revascularization was unsuccessful or not possible. Nonetheless, there is limited evidence of its benefit. The main objective was to evaluate the effectiveness of iloprost and the secondary objective was to evaluate its safety. METHODS: In this cohort study including CLI patients from the COPART registry from 2006/10 to 2021/01, patients exposed to iloprost were matched with up to three unexposed patients according to age, sex, and Propensity Score (PS) for exposure to iloprost. The main outcome combined the occurrence of all-cause death and major amputations; survival was assessed over one-year using Kaplan-Meier estimates and Cox model analyses. Major Adverse Cardiovascular Events (MACE) were chosen as the safety outcome; the association with iloprost was estimated using a logistic regression model. RESULTS: Among 1850 CLI patients, 201 were exposed to iloprost (71.6% men; median age: 72 years vs. 72.1%; 75 years for unexposed). In 134 exposed patients matched to 375 unexposed patients, 14 major amputations and 24 deaths occurred in exposed patients (28.4%) vs. 33 and 46 respectively in the unexposed patients (20.9%). The hazard ratio (HR) was of 1.49 (95% Confidence Interval: 1.01-2.20). The association remained in the subgroup of "no option" patients (HR: 1.74; [1.01-2.20]). Regarding safety, 21/201 (10.7%) exposed patients experienced MACE vs. 146/1649 (9.41%) unexposed patients (unadjusted Odds Ratio [OR]: 1.17 [0.72-1.90]; adjusted OR: 1.23 [0.72-2.11]). CONCLUSION: The study did not find any benefit of iloprost in CLI patients and even suggested a deleterious effect.