Background rates of 41 adverse events of special interest for COVID-19 vaccines in 10 European healthcare databases - an ACCESS cohort study.

BACKGROUND: In May 2020, the ACCESS (The vACCine covid-19 monitoring readinESS) project was launched to prepare real-world monitoring of COVID-19 vaccines. Within this project, this study aimed to generate background incidence rates of 41 adverse events of special interest (AESI) to contextualize potential safety signals detected following administration of COVID-19 vaccines. METHODS: A dynamic cohort study was conducted using a distributed data network of 10 healthcare databases from 7 European countries (Italy, Spain, Denmark, The Netherlands, Germany, France and United Kingdom) over the period 2017 to 2020. A common protocol (EUPAS37273), common data model, and common analytics programs were applied for syntactic, semantic and analytical harmonization. Incidence rates (IR) for each AESI and each database were calculated by age and sex by dividing the number of incident cases by the total person-time at risk. Age-standardized rates were pooled using random effect models according to the provenance of the events. FINDINGS: A total number of 63,456,074 individuals were included in the study, contributing to 211.7 million person-years. A clear age pattern was observed for most AESIs, rates also varied by provenance of disease diagnosis (primary care, specialist care). Thrombosis with thrombocytopenia rates were extremely low ranging from 0.06 to 4.53/100,000 person-years for cerebral venous sinus thrombosis (CVST) with thrombocytopenia (TP) and mixed venous and arterial thrombosis with TP, respectively. INTERPRETATION: Given the nature of the AESIs and the setting (general practitioners or hospital-based databases or both), background rates from databases that show the highest level of completeness (primary care and specialist care) should be preferred, others can be used for sensitivity. The study was designed to ensure representativeness to the European population and generalizability of the background incidence rates. FUNDING: The project has received support from the European Medicines Agency under the Framework service contract nr EMA/2018/28/PE.

Risk of ischemic stroke associated with non-steroidal anti-inflammatory drugs and paracetamol: a population-based case-control study.

OBJECTIVE: To assess the risk of non-fatal ischemic stroke associated with non-steroidal anti-inflammatory drugs (NSAIDs) and paracetamol. The effects of dose, duration of treatment, background cardiovascular (CV) risk and use of concomitant aspirin were studied. METHODS: We performed a population-based case-control study. Patients were considered exposed if they were on treatment within a 30-day window before the index date. We estimated adjusted odds ratios (ORs) and their 95% confidence intervals (CIs) using logistic regression. RESULTS: Two thousand eight hundred and eighty-eight cases and 20 000 controls were included. No increased risk was observed with traditional NSAIDs as a group (OR = 1.03; 95% CI, 0.90-1.19), but results varied across individual agents and conditions of use. An increased risk was found with diclofenac (OR = 1.53; 95% CI, 1.19-1.97), in particular when used at high doses (OR = 1.62; 1.06-2.46), over long-term periods (> 365 days; OR = 2.39; 1.52-3.76) and in patients with a high background CV risk (OR = 1.78; 1.23-2.58), as well as with aceclofenac when used at high doses (OR = 1.67; 1.05-2.67), in long-term treatments (OR = 2.00; 1.14-3.53) and in patients with CV risk factors (OR = 2.33; 1.40-3.87). No association was found with ibuprofen (OR = 0.94; 0.76-1.17) or naproxen (OR = 0.68; 0.36-1.29). The concomitant use of aspirin did not show a significant effect modification. Paracetamol did not increase the risk overall (OR = 0.97; 0.85-1.10) or in patients at high CV risk (OR = 0.94; 0.78-1.14). CONCLUSIONS: Diclofenac and aceclofenac increase the risk of ischemic stroke while ibuprofen and naproxen do not. Dose, duration and baseline CV risk, but not aspirin use, appear to modulate the risk. Paracetamol does not increase the risk, even in patients with a high background CV risk.

[Evaluation of inappropriate prescribing according to Beers criteria in cardiology and respiratory medicine departments]. / Evaluación de las prescripciones inapropiadas según los criterios de Beers en los servicios de cardiología y neumología hospitalarios.

OBJECTIVE: To determine the incidence of potentially inappropriate prescriptions (PPI) for patients older than 65 years admitted to the cardiology and respiratory medicine units, as well as the main drugs involved and their clinical severity. METHODS: A prospective, observational study was carried out over a 6 month period. We reviewed the treatment of patients over 65 years old admitted to these units. PPI is considered as those included in the Beers criteria 2003. We recorded clinical unit, age, sex, inappropriate drug, dosage and route of administration. We calculated the overall incidence of PPI (number of PPI/number of patients) and according to the clinical unit, sex, drug involved, and clinical severity. RESULTS: Data were collected from 385 patients (190 in cardiology and 195 respiratory medicine unit). We found 111 PPI (0.29 PPI/patient). If we take into account the clinical unit, there were 53 PPI in cardiology (0.28 PPI/patient) and 58 PPI in respiratory medicine (0.30 PPI/patient). Two-thirds (66.6%, n=74) of the PPI occurred in men and 33.4% (n=37) in women. The main drugs involved were amiodarone (24.3%), digoxin (19.8%), doxazosin (17.1%) and diazepam (16.2%). According to the Beers criteria, 68.5% of those were high severity PPI. CONCLUSION: The prescription of inappropriate medications in the elderly is high. This is important because they are a cause of adverse reactions, which leads to a significant proportion of hospital admissions. The inclusion of warnings in the program of assisted prescribing and distributing of newsletters about these to the personnel involved, improves the quality of health care and minimises medication-related problems.