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Background: There are few publications regarding manifestations of vestibular disorders (VDs) following BNT162b2 mRNA COVID‐19 vaccination. Purpose: We describe cases of VD potentially related to BNT162b2 vaccination and calculate its reporting rate, in order to enlarge knowledge about this adverse effect. Methods: A retrospective analysis of cases of VD following BNT162b2 vaccination reported to the pharmacovigilance centre of Georges‐Pompidou European Hospital (France), in 2021 was performed. In order to identify these cases from the pharmacovigilance database containing all our registered cases, we used the Standardised MedDRA Query (SMQ) 'vestibular disorders'. Then we analysed cases with vestibular symptoms, based on the association of typical manifestations. The reporting rate was calculated based on the number of VD cases and the number of vaccinated patients. Results: Among 6608 cases reported to our centre related to COVID‐19 vaccines during 2021, 34 VDs associated with BNT162b2 administration were included. They were mainly reported in females (79%), 62% occurred after the first dose and 32% were serious. Symptoms had completely resolved in 13 cases (38%). Vertigo was the most common symptom followed by balance disorders. Three patients received second dose without reappearance of VD. The final diagnosis was reported in 10 patients (six cases of vestibular neuritis, two cases of central VD, two cases of benign paroxysmal positional vertigo). The regional reporting rate was 26 [95% CI: 17–34] cases of VD per 1 million persons vaccinated. Conclusion: Although the relationship between vaccination and VD cannot be established, clinicians should be aware of this rare adverse effect. [ABSTRACT FROM AUTHOR]

The distribution of genetic mutations affects seven out of 20 patients (35%), mainly related to I TP53 i (six patients, 30%), I TET2 i (two patients, 10%) and I DNMT3A i (two patients, 10%). During the long-term follow-ups of randomized controlled trials (RCTs), some cases of therapy-associated myeloid neoplasms (t-MNs), including myelodysplastic syndrome (t-MDS) and acute myeloid leukaemia (t-AML), were reported both in the poly(ADP-ribose)polymerase inhibitors (PARPi) and control arms. For the 21 patients, t-MNs occurred after a median latency period of 18-2 (IQR 10-0-30-0) months following first PARPi exposure. Among them, 113 out of 32 662 patients (0-3%) with OC experienced t-MNs after a mean time from first primary cancer diagnosis of 5-3 years for t-MDS ( I n i = 47 patients) and 4-5 years for t-AML ( I n i = 66 patients), with an overall standardized incidence ratio of 5-8 (4-8-6-9).8 Our shorter latency may be linked to an underlying clonal haematopoiesis as I TET2 i and I DNMT3A i mutations were frequently found. [Extracted from the article]

Objective: Toxicological analysis (TA) is advised when assessing the prognosis and the treatment of drug overdose patients. Apart from this use, the value of TA has remained unclear. This study aimed at defining the value of TA regarding the toxicological diagnosis in severe overdose cases that involved addictive or recreational drugs (ARDs) that were used either alone or in combination with medicinal drugs. Methods: The patients who were enrolled in the study had been admitted to our intensive care unit for the treatment of poisoning. TA was performed using advanced technologies such as mass spectrometry of blood/urine on admission. An occurrence indicated the supposed ingestion of a defined substance. Patients were included in a group depending on the combination of the occurrences of supposed ingested drugs (SID) and the results of the 1) TA: SID+, TA+; 2) SID+, not searched by TA; 3) SID-, TA+. Results: There were 224 occurrences of 90 substances in 70 patients. ARDs were present in 30 patients (43%). ARD accounted for 24 occurrences in the SID+, TA+ group, 10 occurrences in the SID+, not searched group and 196 occurrences in the SID-, TA+ group. In the SID+, TA+ group, 9 occurrences (69%) of ethanol were confirmed by TA. Ingestion of ethanol was invalidated in 4 occurrences (31%). In the patients who denied ethanol ingestion, TA confirmed the non-ingestion of ethanol using 30 blood measures (81%). Ethanol was involved in 57% of the patients, being the lone substance in only 1 case. Conclusion: In drug overdose instances that result in organ failure(s) and involve ARDs, self-reporting is of limited value in assessing the patients' exposure to ARD. Multiple consumptions expose patients to unexpected drug interactions. [ABSTRACT FROM AUTHOR]

Summary Parasomnias and sleep‐related movement disorders (SRMD) are major causes of sleep disorders and may be drug induced. The objective of this study was to conduct a systematic review of the literature to examine the association between drug use and the occurrence of parasomnias and SRMD. Following Preferred Reporting Items for Systematic Reviews and Meta‐Analyses guidelines for reporting systematic reviews, we searched PubMed databases between January 2020 and June 2023. The searches retrieved 937 records, of which 174 publications were selected for full‐text screening and 73 drugs were identified. The most common drug‐induced parasomnias were nightmares and rapid eye movement (REM) sleep behaviour disorders and sleepwalking. In terms of drug‐induced SRMD, restless legs syndrome, periodic limb movement disorders (PLMD), and sleep‐related bruxism were most frequent. Medications that inhibit noradrenergic, serotonergic, or orexin transmission could induce REM sleep (e.g., nightmares). Regarding sleepwalking, dysregulation of serotoninergic neurone activity is implicated. Antipsychotics are mentioned, as well as medications involved in the gamma‐aminobutyric acid (GABA) pathway. A mechanism of desensitisation‐autoregulation of GABA receptors on serotoninergic neurones is a hypothesis. SRMD and PLMD could involve medications disrupting the dopamine pathway (e.g., antipsychotics or opioids). Opioids would act on mu receptors and increase dopamine release. The role of adenosine and iron is also hypothesised. Regarding bruxism, the hypotheses raised involve dysregulation of mesocortical pathway or a downregulation of nigrostriatal pathway, related to medications involving dopamine or serotonin. Parasomnias are rarely identified in drug product labels, likely due to the recent classification of their diagnoses. An analysis of pharmacovigilance data could be valuable to supplement existing literature data. [ABSTRACT FROM AUTHOR]

Introduction: Intravenous iron infusion may be complicated by extravasation and lead to cutaneous pigmentation., Methods: We queried the French pharmacovigilance database to assess the spontaneously reported cases over the 2000-2016 period., Results: Fifty-one cases of cutaneous pigmentation related to intravenous iron extravasation were retrieved, none was associated to necrosis. Most of patients were women aged 20 to 49 years old. The pigmentation was mostly a brown coloration, persisting over one month in 19 cases (37.2%) and over 6 months in 9 cases (17.6%). The management of extravasation and pigmentation was heterogeneous and was rarely followed by a decrease of the coloration., Conclusion: Cutaneous pigmentation after intravenous iron extravasation can persist over time and create an aesthetic prejudice, particularly in young women. Standardized extravasation and iron-induced pigmentation management procedures appear necessary., (Copyright © 2017 Société française de pharmacologie et de thérapeutique. Published by Elsevier Masson SAS. All rights reserved.)

Automated signal generation aims to focus the attention of pharmacovigilance experts on drug-ADR associations which are disproportionally present in a spontaneous reporting system. Since 1986, we could find several signals using classic pharmacovigilance techniques with case reports registered in our pharmacovigilance regional centre. From this dataset 3,324 cases were related to spontaneous reporting. Drug-ADR associations were generated by using a Data Mining Algorithm (DMA) proposed by Evans et al. Potential signals were evaluated by reviewing case reports related to the unlabelled associations. The DMA generated 523 associations of which 107 were not described in the SPC. Most potential signals were false positives. Although the DMA generated little additional knowledge compared to signals already detected using classic techniques, the whole process helped us to focus our case review on a very small subset of the whole dataset (9.6%).