In recent clinical trials some cardiac arrhythmias were reported with use of remdesivir for COVID-19. To address this safety concern, we investigated whether use of remdesivir for COVID-19 is ...associated with an increased risk of bradycardia.
Using VigiBase®, the World Health Organization Global Individual Case Safety Reports database, we compared the cases of bradycardia reported in COVID-19 patients exposed to remdesivir with those reported in COVID-19 patients exposed to hydroxychloroquine, lopinavir/ritonavir, tocilizumab or glucocorticoids. All reports of patients with COVID-19 registered up to the 23 September 2020 were included. We conducted disproportionality analyses allowing the estimation of reporting odds ratios (RORs) with 95% CI.
We found 302 cardiac effects including 94 bradycardia (31%) among the 2603 reports with remdesivir prescribed in COVID-19 patients. Most of the 94 reports were serious (75, 80%), and in 16 reports (17%) evolution was fatal. Compared with hydroxychloroquine, lopinavir/ritonavir, tocilizumab or glucocorticoids, the use of remdesivir was associated with an increased risk of reporting bradycardia (ROR 1.65; 95% CI 1.23–2.22). Consistent results were observed in other sensitivity analyses.
This post-marketing study in a real-world setting suggests that the use of remdesivir is significantly associated with an increased risk of reporting bradycardia and serious bradycardia when compared with the use of with hydroxychloroquine, lopinavir/ritonavir, tocilizumab or glucocorticoids. This result is in line with the pharmacodynamic properties of remdesivir.
Population-based data on the epidemiology of progressive multifocal leukoencephalopathy, its predisposing conditions and mortality rate are lacking, although such data are crucial to raise awareness ...among clinicians and to lay foundations for future therapeutic trials in immunomodulating therapies. In our study, patients were identified by interrogating the French national healthcare reimbursement database from 1 January 2008 to 31 December 2017, using progressive multifocal leukoencephalopathy International Classification of Diseases code and a patient's selection algorithm. Overall incidence rate, 1-year all-cause mortality rate and survival patterns were calculated, and factors associated with death were identified using a multivariate Cox proportional hazards regression model. Our cohort is the largest to date, comprising 584 patients with incident progressive multifocal leukoencephalopathy. The overall incidence in France from 2010 to 2017 was stable during the study period at 0.11 per 100 000 person-years, 95% confidence interval 0.10-0.12. Predisposing diseases were HIV infection (43.7%), followed by haematological malignancies (21.9%), chronic inflammatory diseases (20.2%), solid organ transplantation (4.3%), solid neoplasm (4.1%) and primary immune deficiency (1.5%). The 1-year mortality rate was 38.2%, with a 95% confidence interval (34.2-42.2). In multivariate analysis, factors independently associated with death were older age adjusted hazard ratio 0.33 (0.20-0.53) for patients aged 20 to 40 compared with patients aged over 60, male gender adjusted hazard ratio 0.73 (0.54-0.99) for females compared with males and predisposing immunosuppressive disease, with the highest risk for solid neoplasms adjusted hazard ratio 4.34 (2.25-8.37), followed by haematological malignancies adjusted hazard ratio 3.13 (1.85-5.30) and HIV infection adjusted hazard ratio 1.83 (1.12-3.00), compared with chronic inflammatory diseases. Immune reconstitution inflammatory syndrome was notified in 7.0% of patients. In conclusion, incidence of progressive multifocal leukoencephalopathy is stable in France, and HIV infection remains the main predisposing disease. This large-size cohort uncovers a higher risk of mortality for male patients compared to females, and the worst prognosis for patients with solid neoplasm, while prognosis in patients with haematological malignancies appeared less dismal than in previous studies.
Aims
Adverse drug reactions (ADRs) are important causes of death. However, the main involved drugs are relatively unknown. The present study was performed to characterise death‐related drugs recorded ...in a large pharmacovigilance database during the last 10 years.
Methods
A retrospective analysis of VigiBase, the World Health Organization pharmacovigilance database, was performed investigating fatal ADRs registered between 1 January 2010 and 31 December 2019 in male and female patients aged ≥18 years and reported by physicians. Analyses were descriptive investigating age, sex and suspected drugs. Differences in reporting according to sex, age and continents were investigated using disproportionality analysis with calculation of reporting odds ratio and its 95% confidence interval.
Results
Among the 23 millions ADRs recorded in VigiBase, 3 250 967 were included with 43 685 fatal. They were reported mainly in patients older than 75 years. The 3 most frequently involved drug classes were antineoplastic/immunomodulating drugs followed by nervous system and cardiac drugs. The top 3 individual drugs were denosumab, lenalidomide and thalidomide with marked differences according to age, sex, continents and countries. The risk of reporting fatal ADRs was higher in males, in the Americas and in patients ≥65 years.
Conclusion
Fatal ADRs registered in a large pharmacovigilance database during the last 10 years correspond to just over 1% of the total number of ADRs. They occurred more in males, after 65 years and with antineoplastic/immunomodulating drugs in general. Our study also highlighted, for the first time, important differences in fatal ADRs between continents and countries.
To examine associations between polypharmacy and delirium diagnosed in elderly patients hospitalized in geriatric acute care unit after emergency hospital admission.
Study design was an observational ...cohort study in the acute geriatric care unit of a university hospital. We included 410 consecutive patients admitted to the acute geriatric ward during 9 months. Within 72 hours of each patient's hospitalization, a clinically trained geriatrician collected the following data: sociodemographic details (age, sex, type of residence), predisposing factors for delirium, main cause of hospitalization, and current medications. Polypharmacy was defined as 6 or more drugs a day. Delirium was assessed by a geriatrician using the Confusion Assessment Method and was diagnosed on the basis of clinical history with an acute change in usual functional status, behavioral observation, and clinical and cognitive assessment.
Nearly 25% of hospitalized patients had delirium. The Confusion Assessment Method was positive in 69% of patients receiving polypharmacy and in 30% of those not receiving polypharmacy, a relative risk of 2.33. The proportion of elderly patients receiving polypharmacy was 58.53%.
In our study, polypharmacy is an independent risk factor for delirium in a population of elderly patients after emergency admission. In the geriatric population, delirium is an underestimated scourge and because of its medicosocial and economic consequences and its impact on morbidity and mortality, we need to give increased attention to the prevention and control of polypharmacy, which is a predisposing factor for delirium.
Rationale
While meta-analyses of clinical trials found that lurasidone and partial dopamine agonists (brexpiprazole and aripiprazole) were the antipsychotics less likely to cause QTc prolongation, ...and sertindole, amisulpride, and ziprasidone were the most frequently associated with this adverse drug reaction; no real-world studies have investigated this risk between the different antipsychotics.
Objectives and methods
Using data recorded from 1967 to 2019 in VigiBase®, the World Health Organization’s Global Individual Case Safety Reports database, we performed disproportionality analysis to investigate the risk of reporting QT prolongation between 20 antipsychotics.
Results
Sertindole had the highest risk of reporting QT prolongation, followed by ziprasidone and amisulpride. Lurasidone was associated with the lowest risk. First-generation antipsychotics were associated with a greater QT prolongation reporting risk (ROR, 1.21; 95%CI, 1.10–1.33) than second-generation antipsychotics. A positive correlation was found between the risk of reporting QT prolongation and affinity for hERG channel (
R
2
= 0.14, slope = Pearson coefficient = 0.41,
p
value = 0.1945).
Conclusions
This large study in a real-world setting suggests that sertindole and ziprasidone were the antipsychotics drugs associated with the highest risk of QT prolongation reporting. Our results suggest that lurasidone is less associated with QT interval prolongation reports. Our study also suggests that antipsychotics with the higher hERG affinity are more associated with to QT prolongations reports.
Aim:
To compare different β-adrenoceptor antagonists for the risk of reporting nightmare.
Methods:
The study involved two approaches: first, we investigated in VigiBase®, the World Health ...Organization Individual Case Safety Report (ICSR) database, the disproportionality between exposure to each β-adrenoceptor antagonists and reports of nightmares between 1967 and 2019. Second, in a pharmacoepidemiological–pharmacodynamic analysis, we assessed whether use of β-adrenoceptor antagonists with moderate and high lipid solubility or strong 5-HT1A affinity were associated with an increased risk of reporting nightmares. We conducted multivariate logistic regression to estimate reporting odds ratios (RORs) of nightmares compared to all other adverse drug reactions.
Results:
Of the 126,964 reports recorded with β-adrenoceptor antagonists, 1138 (0.9%) were nightmares. The highest risk of reporting a nightmare was found with exposure of pindolol (adjusted ROR 2.82, 95%CI, 2.19–3.61), metoprolol (1.89, 1.66–2.16), and alprenolol (1.77, 1.06–2.97). Compared to use of low lipid solubility β-adrenoceptor antagonists, use of moderate or high lipid solubility β-adrenoceptor antagonists were significantly more associated with nightmare reports (aROR moderate vs. low 1.72, 95%CI 1.47–2.00 and aROR high vs. low 1.84, 95%CI 1.53–2.22). Use of moderate or high 5-HT1A affinity of β-adrenoceptor antagonists was associated with an increased ROR of nightmares compared with low 5-HT1A affinity of β-adrenoceptor antagonists (aROR moderate vs. low 1.22, 95%CI 1.04–1.43 and aROR high vs. low 2.46, 95%CI 1.93–3.13).
Conclusion:
In our large pharmacovigilance study, nightmares are more frequently reported for pindolol and metoprolol, and among β-adrenoceptor antagonists with high lipid solubility and high 5-HT1A receptor affinity.
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