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Transverse myelitis (TM) has recently been associated by health authorities with Ad26.COV2.S (Janssen/JohnsonJohnson), one of the 5 US Food and Drug Administration (FDA) or European Medicines Agency (EMA) labeled severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) vaccines. It is unknown whether a similar association exists for the other FDA or EMA labeled SARS-CoV-2 vaccines (BNT162b2 [Pfizer/BioNTech], mRNA-1273 [Moderna], ChAdOx1nCov-19 [Oxford-AstraZeneca], and NVX-CoV2373 [Novavax]). This study aimed to evaluate the association between SARS-CoV-2 vaccine class and TM.This observational, cross-sectional, pharmacovigilance cohort study examined individual case safety reports from VigiBase, the World Health Organization's pharmacovigilance database. We first conducted a disproportionality analysis with the information component (IC) using the reports of TM that occurred within 28 days following exposure to the FDA or EMA labeled SARS-CoV-2 vaccines, from December 1, 2020 (first adverse event related to a SARS-CoV-2 vaccine) to March 27, 2022. Second, we analyzed the clinical features of SARS-CoV-2 vaccine-associated TM cases reported in VigiBase.TM was significantly associated both with the messenger ribonucleic acid (mRNA)-based (n = 364; ICFindings from this observational, cross-sectional pharmacovigilance study showed that mRNA-based and vector-based FDA/EMA labeled SARS-CoV-2 vaccines can be associated with TM. However, because TM remains a rare event, with a previously reported rate of 0.28 cases per 1 million vaccine doses, the risk-benefit ratio in favor of vaccination against SARS-CoV-2 virus remains unchallenged. Rather, this study suggests that clinicians should consider the diagnosis of TM in patients presenting with early signs of spinal cord dysfunction after SARS-CoV-2 vaccination. ANN NEUROL 2022;92:1080-1089.

Due to their central mechanism of action, antiseizure medications (ASMs) could lead to adverse effects likely to impair driving skills. Their extended use to neuropsychiatric disorders makes it a class of drugs to monitor for their road traffic accidental (RTA) potential. We aimed to assess the reporting association between ASMs and RTAs using the World Health Organization pharmacovigilance database (VigiBase).We performed a disproportionality analysis to compute adjusted reporting odds ratios to evaluate the strength of reporting association between ASMs and RTAs. A univariate analysis using the reporting odds-ratio was used to assess drug-drug interactions between ASMs and RTAs.There were 1 341 509 reports associated with at least 1 ASM in VigiBase of whom 2.91‰ were RTAs reports. Eight ASMs were associated with higher reporting of RTAs compared to others (ranging from 1.35 [95% confidence interval 1.11-1.64] for lamotrigine to 4.36 [95% confidence interval 3.56-5.32] for cannabis). Eight significant drug-drug interactions were found between ASMs and the onset of RTA, mainly involving CYP450 induction.A significant safety signal between RTAs and some ASMs was identified. Association of several ASMs might further increase the occurrence of RTA. ASMs prescription in patients with identified risk factors of RTA should be considered with caution. Study number: ClinicalTrials.gov, NCT04480996.

Hypertension (HTN) is a well-established and a major risk factor for cardiovascular disease. Lifestyle behaviours for its prevention and control are recommended within worldwide guidelines. Their relationship with HTN need more investigations.We aimed to investigate the associations between lifestyle, anthropometric and biological measurements and BP in the Gubbio residential study.Cross-sectional analyses were performed using data from Gubbio study. Information concerning lifestyle factors were collected using self-reported questionnaire and were further completed with a baseline clinical examination and blood exams. Three BP measurements were performed following a standard protocol. Age-adjusted and multivariable logistic regressions were used to examine the relationships between lifestyle parameters and HTN separately for each sex. We used heterogeneity test to observe sex differences.There were 3,183 persons included (48% men, 43 ± 17 years old). Mean systolic BP (SBP) was 119 ± 16 mmHg and 10.6% were hypertensives. Age [OR: 129.70 (95%CI: 18.57-905.79) in women and OR: 8.37 (95%CI: 4.01-17.48) (In addition to age, BMI is associated with HTN in both sexes while sex differences were observed in the associations between serum uric acid, fasting blood glucose and HTN.

Immune-checkpoint inhibitor-associated myocarditis (ICI-myocarditis) often presents with arrhythmias, but the prognostic value of early electrocardiogram findings is unclear. Although ICI-myocarditis and acute cellular rejection (ACR) following cardiac transplantation use similar treatment strategies, differences in arrhythmia burden are unknown.To evaluate the association of electrocardiogram findings in ICI-myocarditis with myocarditis-related mortality and life-threatening arrhythmia.A total of 125 cases of ICI-myocarditis were identified retrospectively across 49 hospitals worldwide; 50 cases of grade 2R or 3R ACR were included as comparators. Two cardiologists blinded to clinical data interpreted electrocardiograms. Associations between electrocardiogram features, myocarditis-related mortality and the composite of myocarditis-related mortality and life-threatening arrhythmias were examined. Adjusted hazard ratios (aHRs) were calculated.The cohort had 78 (62.4%) men; median (interquartile range) age was 67 (58-76) years. At 30 days, myocarditis-related mortality was 20/124 (16.1%), and 28/124 (22.6%) met the composite endpoint. Patients who developed complete heart block (aHR by subdistribution hazards model [aHR(sh)] 3.29, 95% confidence interval [CI] 1.24-8.68; P=0.02) or life-threatening cardiac arrhythmias (aHR(sh) 6.82, 95% CI: 2.87-16.21; P0.001) had a higher risk of myocarditis-related mortality. Pathological Q waves (aHR(sh) 3.40, 95% CI: 1.38-8.33; P=0.008), low QRS voltage (aHR(sh) 6.05, 95% CI: 2.10-17.39; P0.001) and Sokolow-Lyon index (aHR(sh)/mV 0.54, 95% CI: 0.30-0.97; P=0.04) on admission electrocardiogram were also associated with increased risk of myocarditis-related mortality. These associations were mirrored in the composite outcome analysis. Compared with ACR, ICI-myocarditis had a higher incidence of life-threatening cardiac arrhythmias (15/125 [12.0%] vs 1/50 [2%]; P=0.04) and third-degree heart block (19/125 [15.2%] vs 0/50 [0%]; P=0.004).Electrocardiograms in ICI-myocarditis with ventricular tachycardias, heart block, low-voltage and pathological Q waves were associated with myocarditis-related mortality and life-threating arrhythmia. Arrhythmia burden in ICI-myocarditis exceeds that of ACR after heart transplant.

Acquired hemophilia A (AHA) is a rare autoimmune hemorrhagic disease occurring in several underlying conditions. Drug-associated AHA (D-AHA) is poorly addressed nowadays.This work aims to identify and characterize which drugs are associated with AHA using the WHO global database of reported potential effects of medicinal products (VigiBase).First, we realized a disproportionality analysis using the information component (IC) to identify D-AHA in VigiBase. IC compares observed- and expected-values in order to find associations between drugs and adverse drug reactions (ADRs) using disproportionate Bayesian reporting. IC14 drugs with ICThis worldwide pharmaco-epidemiologic study updates the list of the drugs associated with AHA. The clinician should be aware of these possible severe ADR, which might require larger epidemiological and pathophysiologic studies.

The risk of cancer associated with persons with multiple sclerosis (pwMS) prescribed with disease modifying therapies (DMTs) is not well established. This observational, cross-sectional, pharmacovigilance cohort study examined individual case safety reports from the World Health Organization database: VigiBase®. All consecutive reports of DMTs prescribed to pwMS (alemtuzumab, dimethyl fumarate, fingolimod, glatiramer acetate, interferon-β, natalizumab, ocrelizumab, and teriflunomide), and their serious adverse event cases were eligible, excluding those reporting immunosuppressant DMTs used as anticancer therapies. The primary outcome was the multivariate odds ratio of cancer reporting (r-OR) for DMTs prescribed to pwMS after imputation of missing data. There were 5966 cancer cases from 240,993 reports of DMTs prescribed to pwMS. After adjustments on age, sex, and geographical region, natalizumab (r-OR 1.74, 95% CI 1.63–1.87), interferon-β (r-OR 1.39, 95% CI 1.30–1.49), dimethyl fumarate (r-OR 1.35, 95% CI 1.25–1.46), and fingolimod (r-OR 1.15, 95% CI 1.06–1.24) were significantly associated with a greater cancer reporting, whereas alemtuzumab, glatiramer acetate, ocrelizumab, and teriflunomide were not, in the disproportionality analysis. As exploratory analyses, upper aerodigestive tract, breast, urinary including the male genitourinary tract, and nervous system cancers were associated with natalizumab, interferon-β, and dimethyl fumarate. Fingolimod was only associated with skin cancer types. Cancer cases reporting these four DMTs prescribed to pwMS were younger in age than for non-pwMS drugs in the VigiBase® (p

International audience; Purpose: Immune checkpoint blocker (ICB) associated myocarditis (ICB-myocar-ditis) may present similarly and/or overlap with other cardiac pathology including acute cor-onary syndrome presenting a challenge for prompt clinical diagnosis.Methods: An international registry was used to retrospectively identify cases of ICB-myocarditis. Presence of coronary artery disease (CAD) was defined as coronary artery steno-sis >70% in patients undergoing coronary angiogram.Results: Among 261 patients with clinically suspected ICB-myocarditis who underwent a coro-nary angiography, CAD was present in 59/261 patients (22.6%). Coronary revascularization was performed during the index hospitalisation in 19/59 (32.2%) patients. Patients undergoing coro-nary revascularization less frequently received steroids administration within 24 h of admission compared to the other groups (p = 0.029). Myocarditis-related 90-day mortality was 9/17 (52.7%) in the revascularised cohort, compared to 5/31 (16.1%) in those not revascularized and 25/156 (16.0%) in those without CAD (p = 0.001). Immune-related adverse event-related 90-day mortality was 9/17 (52.7%) in the revascularized cohort, compared to 6/31 (19.4%) in those not revascularized and 31/156 (19.9%) in no CAD groups (p = 0.007). All-cause 90-day mortality was 11/17 (64.7%) in the revascularized cohort, compared to 13/31 (41.9%) in no revas-cularization and 60/158 (38.0%) in no CAD groups (p = 0.10). After adjustment of age and sex, coronary revascularization remained associated with ICB-myocarditis-related death at 90 days (hazard ratio [HR] = 4.03, 95% confidence interval [CI] 1.84-8.84, p < 0.001) and was margin-ally associated with all-cause death (HR = 1.88, 95% CI, 0.98-3.61, p = 0.057).Conclusion: CAD may exist concomitantly with ICB-myocarditis and may portend a poorer outcome when revascularization is performed. This is potentially mediated through delayed diag-nosis and treatment or more severe presentation of ICB-myocarditis.

The pathophysiological mechanisms involved in systemic sclerosis (SSc), especially the triggering factor, are poorly understood. The literature supporting the role of drugs in the onset of SSc primarily relies on case reports, short series or previous studies of old drugs. We aimed to update the list of suspected drugs associated with SSc (DASSc).Analyzing the World Health Organization (WHO) pharmacovigilance database (Vigibase®), we collected all individual case safety reports (ICSRs) of drugs putatively associated with SSc reported since 1967 using the Medical Dictionary for Regulatory Activities preferred terms "systemic sclerosis" and "scleroderma". For each drug, a disproportionality analysis was performed by calculating the information component (IC). An identified drug was considered significant if the ICA total of 2800 deduplicated ICSRs of DASSc were identified, accounting for 509 ICSRs and 38 suspected DASSc after exclusion of protopathic and indication biases. Anticancer drugs were the most represented drug class, accounting for 16/38 (42%) of DASSc and 317/509 (62.3%) of ICSRs, which occurred mostly in the first years after the introduction of the drugs. Among these, taxane-based agents, bleomycin, vinblastine, imatinib, dacarbazine, pembrolizumab and pemetrexed were associated with the highest disproportionate reporting. Hormone replacement therapy, romiplostim and eculizumab were associated with a significant signal. DASSc was considered a serious adverse drug reaction in 404 (92%, n = 441) cases with 41 (9%) cases resulting in death.Several new drugs with significant disproportionality signals were identified as potential drugs implicated the development of SSc, particularly anticancer drugs.

Background: Checkpoint inhibitors, such as PD-1 inhibitors (nivolumab, pembrolizumab) and anti-CTLA-4 (CD152) (ipilimumab), are widely used in metastatic melanoma, and most immune-related adverse events are known. Several cardiovascular AEs (CVAEs) associated with immune checkpoint inhibitor exposure have been reported in post-marketing surveillance studies and represent major issues for patients with melanoma during and after cancer treatment. Data on CVAES induced by immune checkpoint inhibitors in melanoma, especially incidence and risk factors, are lacking. Methods: A systematic review of the literature up to 31 August 2020 was performed in Medline, the Cochrane Central Register of Controlled Trials (CENTRAL), and the ClinicalTrials.gov register according to prespecified selection criteria from inception to 7 April 2020. Statistics were performed on 3289 patients from five randomized clinical trials on melanoma. Results: Patients with melanoma treated with immune checkpoint inhibitors had a significant risk of presenting dyslipidemia (Peto OR: 4.74, 95% CI: 2.16–10.41, p < 0.01, I2 = 0%, p = 0.94). The Peto OR was numerically significant for pericarditis, myocarditis, heart failure, myocardial infarction, cerebral ischemia, high pulmonary pressure, blood high pressure, arrhythmias, endocarditis, and conduction disturbances, but the confidence interval was not significant. The risk of CVAEs was not statistically different between melanoma treated with immune checkpoint inhibitors and other tumors treated with immune checkpoint inhibitors (range of p-value from 0.13 to 0.95). No interaction between follow-up length and CVAE reporting was found. Conclusions: Our study underlines that checkpoint inhibitors used for melanoma increase CVAEs, especially dyslipidemia, which could pave the way to chronic inflammatory processes, atherosclerosis, and, finally, ischemic cardiopathy. These cardiovascular adverse events could be acute or delayed, justifying the monitoring of lipidic biology and a baseline cardiology consultation.

Summary Background Poly(ADP-ribose) polymerase (PARP) inhibitors have shown efficacy and acceptable safety in a range of neoplasms, particularly in ovarian cancers. However, some concerns have emerged regarding rare and delayed adverse events including cases of myelodysplastic syndrome and acute myeloid leukaemia, for which data are scarce. The aim of this study was to estimate the risk of myelodysplastic syndrome and acute myeloid leukaemia related to PARP inhibitors, via a systematic review and safety meta-analysis, and to describe clinical features of PARP inhibitor-related myelodysplastic syndrome and acute myeloid leukaemia cases reported in WHO's pharmacovigilance database (VigiBase). Methods We systematically reviewed randomised controlled trials (RCTs) comparing PARP inhibitor therapy versus control treatments (placebo and non-placebo) in adults (age ≥18 years) treated for cancer in MEDLINE, the Cochrane Central Register of Controlled Trials, and the ClinicalTrials.gov registry with ongoing surveillance up to May 31, 2020. The date range for included studies was not restricted. By a stepwise method to capture all available adverse events, we first extracted data on myelodysplastic syndrome and acute myeloid leukaemia cases from ClinicalTrials.gov . If cases were not available, we extracted them from published manuscripts, or subsequently contacted corresponding authors or sponsors to provide data. RCTs without available data from ClinicalTrials.gov , publications, or corresponding authors or sponsors were excluded. The primary outcome was the summary risk of myelodysplastic syndrome and acute myeloid leukaemia related to PARP inhibition versus placebo treatment in RCTs. We used a fixed-effects meta-analysis to obtain Peto odds ratios (ORs) with 95% CIs. In a separate observational, retrospective, cross-sectional pharmacovigilance study of VigiBase, cases of myelodysplastic syndrome and acute myeloid leukaemia related to PARP inhibitor therapy were extracted on May 3, 2020, and clinical features summarised with a focus on median duration of PARP inhibitor exposure, median latency period between first drug exposure and diagnosis, and proportion of cases resulting in death. Our systematic review and safety meta-analysis were registered with PROSPERO, CRD42020175050. Our retrospective pharmacovigilance study was registered on ClinicalTrials.gov , NCT04326023 . Findings For our safety meta-analysis, initial searches identified 1617 citations, and 31 RCTs were systematically reviewed for eligibility. 28 RCTs with available adverse events were analysed (18 placebo and ten non-placebo RCTs), with 5693 patients in PARP inhibitor groups and 3406 patients in control groups. Based on the 18 placebo RCTs (n=7307 patients), PARP inhibitors significantly increased the risk of myelodysplastic syndrome and acute myeloid leukaemia compared with placebo treatment (Peto OR 2·63 [95% CI 1·13–6·14], p=0·026) with no between-study heterogeneity (I2=0%, χ2 p=0·91). The incidence of myelodysplastic syndrome and acute myeloid leukaemia across PARP inhibitor groups was 0·73% (95% CI 0·50–1·07; I2=0%, χ2 p=0·87; 21 events out of 4533 patients) and across placebo groups was 0·47% (0·26–0·85; I2=0%, χ2 p=1·00; three events out of 2774 patients). All 28 RCTs were rated as having unclear risk of bias. In VigiBase, 178 cases of myelodysplastic syndrome (n=99) and acute myeloid leukaemia (n=79) related to PARP inhibitor therapy were extracted. In cases with available data, median treatment duration was 9·8 months (IQR 3·6–17·4; n=96) and median latency period since first exposure to a PARP inhibitor was 17·8 months (8·4–29·2; n=58). Of 104 cases that reported outcomes, 47 (45%) resulted in death. Interpretation PARP inhibitors increased the risk of myelodysplastic syndrome and acute myeloid leukaemia versus placebo treatment. These delayed and often lethal adverse events should be studied further to improve clinical understanding, particularly in the front-line maintenance setting. Funding None.

Aim: Mitochondrial dysfunction (MD) has been associated with poor outcomes after coronary artery bypass graft surgery. Methods: 58 consecutive patients from the ALDO-POAF Study (NCT02814903) were prospectively included. Plasma aldosterone was assessed at the time of the preoperative consultation and mitochondrial functional studies were performed using atrial appendage tissue collected during surgery. Results: Patients with the highest preoperative plasma aldosterone level had a lower mitochondrial respiratory chain functioning and a lower calcium retention capacity. Chronic kidney disease, patient’s age and preoperative high-aldosterone were independent predictors of MD in multivariate analysis. Conclusion: These exploratory data support the use of preventive strategies targeting aldosterone and/or mineralocorticoid receptor activation, in order to prevent perioperative MD and associated poor outcomes.

An increase in left ventricular volumes between baseline and follow-up imaging is the main criteria for the quantification of left ventricular remodelling (LVR) after ST-elevation myocardial infarction (STEMI), but without consensual definition. We aimed to review the criteria used for the definition of LVR based on cardiac magnetic resonance imaging (CMR) in STEMI patients. A systematic literature search was conducted using MEDLINE and the Cochrane Library from January 2010 to August 2019. Thirty-seven studies involving 4209 patients were included. Among these studies, 30 (81%) used a cut-off value for defining LVR, with a pooled LVR prevalence estimate of 22.8%, 95% CI [19.4-26.7%] and a major between-study heterogeneity (I2 = 82%). The seven remaining studies (19%) defined LVR as a continuous variable. The definition of LVR using CMR following STEMI is highly variable, among studies including highly selected patients. A 20% increase or a 15% increase in left ventricular volumes between a baseline and a follow-up CMR imaging were the two most common criterion (13 [35%] and 9 [24%] studies, respectively). The most frequent LVR criterion was a 20% increase in end-diastolic volumes or a 15% increase in end-systolic volumes. A composite cut-off value of a 12 to 15% increase in end-systolic volume and a 12 to 20% increase in end-diastolic volume using a follow-up CMR imaging 3 months after STEMI might be proposed as a consensual cut-off for defining adverse LVR for future large-sized, prospective studies with serial CMR imaging and long-term follow-up in unselected patients.

BackgroundClozapine is mainly used in patients with treatment-resistant schizophrenia and may lead to potentially severe haematologic adverse events, such as agranulocytosis. Whether clozapine might be associated with haematologic malignancies is unknown. We aimed to assess the association between haematologic malignancies and clozapine using Vigibase®, the WHO pharmacovigilance database.MethodsWe performed a disproportionality analysis to compute reporting odds-ratio adjusted for age, sex and concurrent reporting of antineoplastic/immunomodulating agents (aROR) for clozapine and structurally related drugs (loxapine, olanzapine and quetiapine) compared with other antipsychotic drugs. Cases were malignant lymphoma and leukaemia reports. Non-cases were all other reports including at least one antipsychotic report.ResultsOf the 140 226 clozapine-associated reports, 493 were malignant lymphoma cases, and 275 were leukaemia cases. Clozapine was significantly associated with malignant lymphoma (aROR 9.14, 95% CI 7.75–10.77) and leukaemia (aROR 3.54, 95% CI 2.97–4.22). Patients suffering from those haematologic malignancies were significantly younger in the clozapine treatment group than patients treated with other medicines (p < 0.001). The median time to onset (available for 212 cases) was 5.1 years (IQR 2.2–9.9) for malignant lymphoma and 2.5 years (IQR 0.6–7.4) for leukaemia. The aROR by quartile of dose of clozapine in patients with haematologic malignancies suggested a dose-dependent association.ConclusionsClozapine was significantly associated with a pharmacovigilance signal of haematologic malignancies. The risk-benefit balance of clozapine should be carefully assessed in patients with risk factors of haematologic malignancies. Clozapine should be used at the lowest effective posology.

Background Patients with cancer admitted for an acute coronary syndrome (ACS) and/or percutaneous coronary intervention (PCI) represent a growing and high-risk population. The influence of co-existing cancer on mortality remains unclear in such patients. We aimed to assess the impact of cancer on early and late, all-cause and cardiac mortality in the setting of ACS and/or PCI. Methods We performed a systematic review and meta-analysis of studies comparing outcomes of patients with and without a history of cancer admitted for ACS and/or PCI. Results Six studies including 294,528 ACS patients and three studies including 39,973 PCI patients were selected for our meta-analysis. Patients with cancer had increased rates of in-hospital all-cause death (RR 1.74 [1.22; 2.47]), cardiac death (RR 2.44 [1.73; 3.44]) and bleeding (RR 1.64 [1.35; 1.98]) as well as one-year all-cause death (RR 2.62 [1.2; 5.73]) and cardiac death (RR 1.89 [1.25; 2.86]) in ACS studies. Rates of long term all-cause (RR 1.96 [1.52; 2.53]) but not cardiac death were higher in cancer patients admitted for PCI. Conclusion Cancer patients represent a high-risk population both in the acute phase and at long-term after an ACS or PCI. The magnitude of the risk of mortality should however be tempered by the heterogeneity among studies. Early and long term optimal management of such patients should be promoted in clinical practice.

Importance In the last decade, immune checkpoint inhibitors (ICIs) have been approved for the treatment of many cancer types. Immune checkpoint inhibitor–associated myocarditis has emerged as a significant and potentially fatal adverse effect. Recognizing, diagnosing, and treating ICI-associated myocarditis poses new challenges for the practicing clinician. Here, the current literature on ICI-associated myocarditis is reviewed. Observations Clinical presentation and cardiac pathological findings are highly variable in patients with ICI-associated myocarditis. Although endomyocardial biopsy is the criterion standard diagnostic test, a combination of clinical suspicion, cardiac biomarkers (specifically troponin), and cardiac imaging, in addition to biopsy, is often needed to support the diagnosis. Importantly, the combination of a cytotoxic T-lymphocyte–associated protein 4 inhibitor with a programmed cell death protein 1 or programmed death-ligand 1 inhibitor increases the risk of developing ICI-associated myocarditis. Conclusion and Relevance This review aims to provide a standardized diagnostic and therapeutic approach for patients with suspected ICI-associated myocarditis. A complete history of recent cancer treatments and physical examination in combination with cardiac biomarkers, cardiac imaging, and endomyocardial biopsy represent a pragmatic diagnostic approach for most cases of ICI-associated myocarditis. The addition of novel biomarkers or imaging modalities is an area of active research and should be evaluated in larger cohorts.

Introduction : La notification spontanee des effets indesirables medicamenteux (EIMs) est un des piliers de la surveillance en post-AMM. Une des principales limites de cette derniere concerne la qualite de l’information de ces notifications.L’objectif principal de cette etude etait d’evaluer l’informativite des observations d’EIMs enregistrees dans la Base Nationale de PharmacoVigilance (BNPV) a partir des declarations des medecins generalistes (MGs). L’objectif secondaire etait d’identifier les facteurs associes a une declaration complete.Methode : Toutes les observations d’EIMs declarees en France, en 2015, par les MGs ont ete extraites. Apres analyse du contenu de ces declarations (EIM, date d’apparition, description clinique, medicament impute, etc.), l’informativite etait analysee a partir de plusieurs criteres obligatoires (âge, genre, EIM et medicament(s) suspecte(s)) et facultatifs (antecedents medicaux, medicaments concomitants, evolution de la symptomatologie et examens complementaires) ; cela a permis de classifier les declarations en « bien renseignee », « moyennement renseignee » et « mal renseignee ».Resultats : Durant l’annee 2015, la BNPV comportait 3 020 declarations realisees par les MGs francais. Seulement 16,4 % des declarations de pharmacovigilance rapportees etaient « bien renseignees ». Les criteres les moins bien documentes etaient les medicaments concomitants (41,4 %) et les examens complementaires (37,4 %). Les observations completes etaient associees a la gravite des cas (OR = 3,02 [IC 95 % 2,44 ; 3,23], p

Monoclonal antibodies are therapeutic monoclonal Ig that act by highly specific binding to their target antigen and by interacting with the immune system. Their side effects are mainly related to their mechanism of action. The most frequent adverse effects are infusion reactions. Post-marketing surveillance is essential for identifying adverse reactions and improving knowledge of their mechanism of action.

Background and aim Evidences suggest that androgen deficiency is associated with sudden cardiac death (SCD). Our purpose was to analyse some electrocardiographic (ECG) markers of repolarization phase in hypogonadal patients either at baseline or after testosterone replacement therapy (TRT). Patients and Methods Baseline and after 6 months of testosterone replacement therapy, 14 hypogonadal patients and 10 age-matched controls underwent a short-term ECG recordings at rest and immediately after a maximal exercise test. The following ECG parameters have been collected: QTe (the interval between the q wave the end of T wave), QTp (the interval between the q wave and the peak of T wave), and Te (the interval between the peak and the end of T wave). Results At baseline, in the hypogonadal patients, corrected QTe and QTp values were longer at rest than in the controls at rest (p < 0.05), whereas, during the recovery phase, only the QTp remained significantly longer (p < 0.05). After TRT, hypogonadal patients showed an improvement only in Te (p < 0.05). Conversely, any difference between hypogonadal patients and control subjects was found with respect to the markers of temporal dispersion of repolarization phases, except for a worse QTp → Te coherence (p = 0.001) obtained during the recovery phase. Conclusions In conclusion, at rest, hypogonadal patients suffer from a stable increase in the myocardial repolarization phase without an increase in its temporal dispersion and, hence, the SCD risk seems to be low.

Drug-induced hypertension was described with several pharmacological classes, especially with serotonin reuptake inhibitors (SRIs). However, this link has remained controversial: the French summary of product characteristics specify a risk of hypertension only with paroxetine and sertraline. To identify a possible class effect common to all SRIs, our study investigated the reports of hypertension associated with SRIs in two pharmacovigilance databases. Two different types of investigations were performed: (i) a comparative study in VigiBase® , which is the World Health Organization (WHO) pharmacovigilance database (PVDB), from where notifications of hypertension with six SRIs (citalopram, escitalopram, fluoxetine, fluvoxamine, paroxetine, sertraline) were extracted. The relationship between the suspected SRIs and the occurrence of hypertension was assessed by calculating reporting odds ratio (ROR) in a case/non-case design; (ii) a descriptive study of hypertension reports associated with SRIs in the French pharmacovigilance database (FPVDB). In VigiBase® , 14 824 notifications of SRI-induced hypertension (2.5%) were identified (mean age 54.3 years, mainly women 69.1%). Among them, 3 879 (26.2%) were associated to sertraline; 3 118 (21.0%) to fluoxetine; 2 725 (18.4%) to paroxetine; 2 570 (17.3%) to citalopram; 2 295 (15.5%) to escitalopram; and 237 (1.6%) to fluvoxamine. A significant ROR value was found with all six SRIs (ROR range from 1.16 to 1.92). In the FPVDB, 24 reports of hypertension were found with all six SRIs used at standard doses, mainly in women (66.7%) with a mean age of 57.8 years and a median time of onset of 6 days. In 10 cases (42%), patients had a history of hypertension. This study, performed in real conditions of life, shows a significant pharmacovigilance safety signal between the use of SRIs and the development or worsening of hypertension.

Dear Editor, Dupilumab is a human monoclonal antibody that blocks the shared receptor unit for interleukin (IL)-4 and IL-13, and is approved in several indications, including moderate-to-severe atopic dermatitis (AD). According to a recent meta-analysis dupilumab treatment versus placebo resulted in a significant increase in the number of patients who achieved Eczema Area and Severity Index-75 (Rate-Ratio 3.09; 95% CI 2.45-3.89) in different ethnical populations.

Aims The risk and incidence of cardiovascular (CV) immune-related adverse events (irAEs) associated with immune checkpoint inhibitors (ICIs) in cancer patients remain unknown. Methods and results We systematically reviewed all randomized clinical trials (RCTs) including at least one ICI-containing arm and available CV adverse event (CVAE) data in cancer patients in the ClinicalTrials.gov registry, Medline, and the Cochrane CENTRAL Register of Controlled Trials, up to 31 August 2020 (CRD42020165672). The primary outcome was the summary risk of 16 different CVAEs associated with ICI exposure vs. controls (placebo and non-placebo) in RCTs. CVAEs with an increased risk associated with ICI exposure were considered as CV irAEs. Summary incidences of CV irAEs identified in our primary outcome analyses were computed using all RCTs including at least one ICI-containing arm. We used a random-effects meta-analysis to obtain Peto odds ratios (ORs) with 95% confidence intervals (CIs) and logit transformation and inverse variance weighting to compute summary incidences. Sixty-three unique RCTs with at least one ICI-containing arm (32 518 patients) were retrieved, among which 48 (29 592 patients) had a control arm. Among the 16 CVAEs studied, ICI use was associated with an increased risk of 6 CV irAEs including myocarditis, pericardial diseases, heart failure, dyslipidemia, myocardial infarction, and cerebral arterial ischaemia with higher risks for myocarditis (Peto OR: 4.42, 95% CI: 1.56–12.50, P Conclusion In RCTs, ICI use was associated with six CV irAEs, not confined to myocarditis and pericarditis.

International audience; No abstract available