Background Due to safety signals after vaccination with COVID-19 vector vaccines, several states recommended to complete the primary immunization series in individuals having received one dose of ChAdOx1 (AstraZeneca) with an mRNA vaccine. However, data on safety and reactogenicity of this heterologous regimen are still scarce. The aim of this study was therefore to compare the reactogenicity and the frequency of medical consultations after boost vaccination in a heterologous regimen with ChAdOx1 and mRNA-vaccines (BNT162b2, BioNTech/Pfizer or mRNA-1273, Moderna) to homologous regimens with ChAdOx1 or mRNA-vaccines, respectively. Methods In an observational cohort study reactogenicity and safety were assessed 14–19 days (short-term) and 40 to 56 days (long-term) after the boost vaccination using web-based surveys. In the short-term survey solicited and unsolicited reactions were assessed, while the long-term survey focussed on health problems leading to medical consultation after the vaccination, including those that were not suspected to be vaccine-related. Results In total, 9146 participants completed at least one of the surveys (ChAdOx1/ChAdOx1: n = 552, ChAdOx1/mRNA: n = 2382, mRNA/mRNA: n = 6212). In the short-term survey, 86% with ChAdOx1/mRNA regimen reported at least one reaction, in the ChAdOx1/ChAdOx1 and mRNA/mRNA cohorts 58% and 76%, respectively (age and sex adjusted p < 0.0001). In the long-term survey, comparable proportions of individuals reported medical consultation (ChAdOx1/ChAdOx1 vs. ChAdOx1/mRNA vs. mRNA/mRNA: 15% vs. 18% vs. 16%, age and sex adjusted p = 0.398). Female gender was associated with a higher reactogenicity and more medical consultations. Younger age was associated with a higher reactogenicity, whereas elderly people reported more medical consultations. Conclusion Although the short-term reactogenicity was higher with the heterologous regimen than with the homologous regimens, other factors such as higher efficacy and limited resources during the pandemic may prevail in recommending specific regimens.

Background For stroke prevention in patients with atrial fibrillation (AF), direct oral anticoagulants (DOACs) have been increasingly prescribed instead of vitamin-K-antagonists (VKA). For some patients a lower dosage of DOACs (ld-DOACs) is recommended. Ld-DOAC prescribing seems to be common, although previous studies did not show clear superiority of ld-DOACs over warfarin. In Germany, phenprocoumon is used almost exclusively as VKA. Randomized controlled trials comparing DOACs and phenprocoumon in the general population of patients with AF do not exist. Therefore, we aimed to compare ld-DOACs and phenprocoumon in a real-world setting in Germany. Methods In a retrospective observational cohort study, claims data from a group of small to medium-sized health insurance companies were analysed. Risks for the outcomes thromboembolism, death and major bleeding were estimated by Cox regression. Out of 93,685 patients with atrial fibrillation and a first prescription of an oral anticoagulant, 20,179 receiving VKA and 21,724 ld-DOACs (29.6% of all DOAC patients) were included. For the sensitivity analysis phenprocoumon was compared to the five ld-DOAC groups (ld-apixaban, ld-dabigatran, ld-edoxaban, ld-rivaroxaban, and the composite of all ld-DOACs) after propensity-score matching. Results Phenprocoumon was associated with statistically significant fewer thromboembolic events (HR = 1.29, 95% CI [1.13, 1.48], p < .001) and deaths (HR = 1.52, 95% CI [1.41, 1.63], p < .001) and a non-significant higher bleeding risk (HR = 0.89, 95% CI [0.79, 1.00], p = .051) than composite ld-DOAC. Regarding the subgroups, only patients with ld-apixaban had a statistically significant higher risk for thromboembolic events (HR = 1.42, 95% CI [1.21, 1.65], p < .001) and a lower bleeding risk (HR = 0.75, 95% CI [0.65, 0.86], p < .001). Ld-apixaban, ld-edoxaban, and ld-rivaroxaban were associated with a higher risk of death. The sensitivity analysis confirmed these associations. Conclusion Phenprocoumon seems to be superior to ld-DOACs for patients with AF. As a hypothesis phenprocoumon might turn out to be the wiser choice for high-risk patients with AF as compared to ld-DOACs, especially regarding thromboembolic events and death. Therefore, RCTs comparing ld-DOACs with phenprocoumon are needed.

Background: The Corona-Vakzin-Konsortium project (CoVaKo) analyses the efficacy and safety of COVID-19 vaccines in a real-world setting and breakthrough infections in Bavaria, Germany. A subproject of CoVaKo aims to identify adverse events of the COVID-19 vaccine and to compare these to adverse events of other vaccines in an online survey. A prior feasibility study was conducted to test study materials for comprehensibility, visual design and motivation to participate and secondly, to test practical implementation and realization in primary care practices and vaccination centres.Methods: A mixed-methods design was used. Three focus groups with general population participants were performed to evaluate the study materials and survey. Second, a test-roll-out was conducted in vaccination centres and primary care practices, which involved implementation and quantitative evaluation of the online survey. Third, interviews were conducted with participating general practitioners and heads of vaccination centres four weeks after the test-roll-out.Results: Parts of the study information and registration form proved incomprehensible in the recruitment material and/or online survey. For example, headings were misleading since the COVID-19 vaccination was overemphasized in the title as compared to other vaccinations. Participants requested more information on the procedure and completion time. In 31 days, 2199 participants who received either a COVID-19 vaccination (99 %) or at least one of the control vaccinations (1 %) registered for the study. Participants (strongly) agreed that the registration process was easy to understand, that all relevant information was provided, the completion time was reasonable and technical framework manageable. Physicians and heads of the vaccination centres perceived the study as easy to integrate into their workflow and most of them were willing to participate in the main study.Conclusions: Our study indicated that capturing adverse events after vaccinations with an online survey is feasible. Testing of materials and surveys provided valuable improvements. Participation of health professionals is important to ensure practicality of the procedures. Flexible adaptation of the study organization to changing structures and requirements is necessary for a successful implementation, especially due to dynamic changes in COVID-19 vaccination strategies.Trial registration: The trial was retrospectively registered at “Deutsches Register Klinischer Studien” (DRKS-ID: DRKS00025881) on Oct 14, 2021.