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.

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.

Pharmacovigilance data mining with methods based on false discovery rates: a comparative simulation study.

The early detection of adverse reactions caused by drugs that are already on the market is the prime concern of pharmacovigilance efforts; the methods in use for postmarketing surveillance are aimed at detecting signals pointing to potential safety concerns, on the basis of reports from health-care providers and from information available in various databases. Signal detection methods based on the estimation of false discovery rate (FDR) have recently been proposed. They address the limitation of arbitrary detection thresholds of the automatic methods in current use, including those last updated by the US Food and Drug Administration and the World Health Organization's Uppsala Monitoring Centre. We used two simulation procedures to compare the false-positive performances for three current methods: the reporting odds ratio (ROR), the information component (IC), the gamma Poisson shrinkage (GPS), and also for two FDR-based methods derived from the GPS model and Fisher's test. Large differences in FDR rates were associated with the signal-detection methods currently in use. These differences ranged from 0.01 to 12% in an analysis that was restricted to signals with at least three reports. The numbers of signals generated were also highly variable. Among fixed-size lists of signals, the FDR was lowered when the FDR-based approaches were used. Overall, the outcomes in both simulation studies suggest that improvement in effectiveness can be expected from use of the FDR-based GPS method.

[Psychiatric adverse effects of fluoroquinolone: review of cases from the French pharmacologic surveillance database]. / Effets indésirables psychiatriques des fluoroquinolones: cas notifiés à la pharmacovigilance française.

INTRODUCTION: Psychiatric adverse effects of fluoroquinolones are known for long, but can sometimes be missed. We analyse cases spontaneously reported to the French pharmacovigilance. METHODS: Cases of psychiatric adverse effects with fluoroquinolones reported to the French pharmacovigilance system were analysed. The studied period was from January 1985 and June 2002. Data analysed included age, sex, adverse effect, fluoroquinolone, seriousness and evolution. RESULTS: Five hundred ninety cases have been reported concerning 273 males and 316 females (sex unknown in 1 case). Mean age was 66 years (median: 70, range: 12-102). The most frequently reported psychiatric adverse effects were confusion (51%), hallucinations (27%), agitation (13%), delusion (12%), insomnia (8%), somnolence (4%) (several adverse effects could be associated in a single patient). Serious cases represented 21.7% (resulting in hospitalisation in most cases). Evolution was favourable in most cases (88.5%), and was unknown in 9.5% of cases. CONCLUSION: The number of cases reported during this period is moderate, but under-reporting probably interferes. The eventuality of this kind of adverse effect with fluoroquinolones should be kept in mind. Dose should be adjusted to renal function, especially in older patients.

Symptomatic bone disorders in HIV-infected patients: incidence in the Aquitaine cohort (1999-2002).

BACKGROUND: Since the inception of highly active antiretroviral therapy (HAART), mortality among HIV-infected patients has decreased, but this has been accompanied by the appearance of several complications. OBJECTIVES: To estimate the incidence of symptomatic bone disorders in HIV-infected patients of the Aquitaine cohort (from south-west France) for the period 1999-2002, and to describe cases. METHODS: We retrospectively studied the records of 2700 patients of the Aquitaine cohort, which was derived from a hospital-based surveillance system of HIV infection in France. All cases of symptomatic bone disorders diagnosed from 1 January 1999 to 30 June 2002 were reviewed. RESULTS: Fourteen cases of bone disorders were diagnosed, eight cases of aseptic osteonecrosis and six cases of severe osteoporosis, representing incidences of 0.3/1000 patient-years [95% confidence interval (CI): 0.14-0.62] and 0.22/1000 patient-years (95% CI: 0.09-0.52), respectively. All patients with aseptic osteonecrosis were male, while all but one with osteoporosis were female. The ages of patients ranged from 36 to 54 years for osteonecrosis and from 39 to 50 for severe osteoporosis. At the time of clinical diagnosis, all patients were treated with nucleoside reverse transcriptase inhibitors (duration of treatment ranging from 19 to 123 months for osteonecrosis and from 46 to 132 months for severe osteoporosis). Ten patients were treated with nonnucleoside reverse transcriptase inhibitors [duration of treatment ranging from 6 to 31 months for osteonecrosis (n=6) and from 4 to 29 months for severe osteoporosis (n=4)]. Thirteen patients were treated with protease inhibitors [duration of treatment ranging from 12 to 62 months for osteonecrosis (n=8) and from 3 to 44 months for severe osteoporosis (n=5)]. All osteonecrosis and five osteoporosis patients had at least one known risk factor or comorbidity associated with the bone disorder occurrence. CONCLUSIONS: In our study, the aetiology of clinical bone disorders seemed to be multifactorial, as almost all the patients had at least one possible risk factor in addition to HAART exposure.