Myocarditis and pericarditis in individuals exposed to the Ad26.COV2.S, BNT162b2 mRNA, or mRNA-1273 SARS-CoV-2 vaccines

IMPORTANCE: There is a high level of public and professional interest related to potential safety issues of the COVID-19 vaccines; however, no serious adverse cardiovascular events were reported in phase 3 randomized controlled trials of their safety and efficacy. Moreover, none of the case series from the United States (US) of these potential complications have been population-based.OBJECTIVES: To estimate the reporting rates of myocarditis and pericarditis in the US using the Vaccine Adverse Event Reporting System (VAERS), and to assess if these adverse events were disproportionally reported among the different COVID-19 vaccines.DESIGN SETTING AND PARTICIPANTS: All cases of myocarditis and pericarditis from VAERS reported up to July 28, 2021.EXPOSURE: Single-dose Ad26.COV2.S, BNT162b2 mRNA, or mRNA-1273 SARS-CoV-2 vaccinations.MAIN OUTCOMES AND MEASURES: Reporting rates were computed by dividing the total number of cases of myocarditis and pericarditis (combined) by the total number of vaccine doses administered. Disproportionality analyses were performed to evaluate disproportional reporting of myocarditis and pericarditis for the Ad26.COV2.S and mRNA-1273 vaccines vs. the BNT162b2 mRNA vaccine.RESULTS: By July 28, 2021, 1392, 699, and 68 cases of myocarditis or pericarditis had been reported out of 1.91, 1.38, and 1.33 million administered doses of the BNT162b2 mRNA, mRNA-1273, and Ad26.COV2.S COVID-19 vaccines, respectively. Median times to event were 3 days, 3 days, and 9 days for the BNT162b2 mRNA, mRNA-1273, and Ad26.COV2.S COVID-19 vaccines. The reporting rates for myocarditis or pericarditis were 0.00073 (95% confidence interval, 95% CI 0.00069-0.00077), 0.00051 (95% CI 0.00047-0.00055), and 0.00005 events per dose (95% CI 0.00004-0.00006) for the BNT162b2 mRNA, mRNA-1273, and Ad26.COV2.S COVID-19 vaccines, respectively. Myocarditis and pericarditis were disproportionally reported following the BNT162b2 mRNA vaccine when compared with the other vaccines, using both disproportionality measures.CONCLUSIONS AND RELEVANCE: We found reporting rates of myocarditis and pericarditis to be less than 0.1% after COVID-19 vaccination. Rates were highest for the BNT162b2 mRNA vaccine, followed by the mRNA-1273 and Ad26.COV2.S, respectively. However, the reporting rates of myocarditis and pericarditis secondary to vaccination remains less common than those seen for SARS-CoV-2 infection.</p

Do women's perceptions of their childbirth experiences change over time?:A six-week follow-up study in a Danish population

Objective: To evaluate how women's perception of the childbirth experience developed during the postpartum period. The secondary aim was to explore how selected birth interventions were subjectively perceived as part of the birth experience. Design: A prospective cohort study comparing childbirth experience, assessed at one and six weeks postpartum, using the Childbirth Experience Questionnaire (CEQ). Setting: A regional hospital in the northern part of Denmark, with 1,400 childbirths annually. Participants: A total of 201 women with low-risk births who gave birth at North Denmark Regional Hospital were included in this study. We included both nulliparous and multiparous women. Measurements and findings: More than 50% of the women changed their perceptions about their childbirth experience after six weeks. After six weeks the overall CEQ score and the domains ‘Participation’ and ‘Professional support’ had a lower CEQ score compared to scores obtained one week postpartum, although differences were small. Induction of labor, augmentation of labor, emergency caesarean section, epidural analgesia, and use of nitrous oxide were associated with a lower CEQ score. Key conclusions: Women assessed their overall birth experience more negatively at six weeks postpartum compared to one week postpartum. Some interventions in the labor process influenced the women's assessment of their experiences negatively. Implications for practice: Paying attention to preventive initiatives to ensure the women a spontaneous birth, if possible, may be essential to create positive perceptions of the childbirth experience

Unstable Angina as a Component of Primary Composite Endpoints in Clinical Cardiovascular Trials:Pros and Cons

BACKGROUND: Unstable angina (UA) is a component of acute coronary syndrome that is only occasionally included in primary composite endpoints in clinical cardiovascular trials. The aim of this paper is to elucidate the potential benefits and disadvantages of including UA in such contexts. SUMMARY: UA comprises <10% of patients with acute coronary syndromes in contemporary settings. Based on the pathophysiological similarities, it is ideal as a part of a composite endpoint along with myocardial infarction (MI). By adding UA as a component of a primary composite endpoint, the number of events and feasibility of the trial should increase, thus decreasing its size and cost. Furthermore, UA has both economic and quality of life implications on a societal and an individual level. However, there are important challenges associated with the use of UA as an endpoint. With the introduction of high-sensitivity troponins, the number of individuals diagnosed with UA has decreased to rather low levels, with a reciprocal increase in the number of MI. In addition, UA is particularly challenging to define given the subjective assessment of the index symptoms, rendering a high risk of bias. To minimize bias, strict criteria are warranted, and events should be adjudicated by a blinded endpoint adjudication committee. KEY MESSAGES: UA should only be chosen as a component of a primary composite endpoint in cardiovascular trials after thoroughly evaluating the pros and cons. If it is chosen to include UA, appropriate precautions should be taken to minimize possible bias

Gastrointestinal bleeding with direct oral anticoagulants in patients with atrial fibrillation and anaemia

Introduction: A high risk of gastrointestinal bleeding has been reported with the use of some direct oral anticoagulants (DOACs). This risk may be of particular concern in individuals with associated anaemia. The aim of this study is to investigate potential differences in the risks of gastrointestinal bleeding and stroke among the four available DOACs in patients with atrial fibrillation (AF) and moderate or severe anaemia.Materials and methods: All Danish patients diagnosed with incident AF who had a baseline haemoglobin measurement and subsequently initiated DOAC therapy between 2012 and 2021 were identified through administrative registries. Only patients with moderate or severe anaemia (N = 7269) were included and evaluated regarding the risk of hospitalization for gastrointestinal bleeding and stroke. Standardized absolute 1-year risks of stroke and gastrointestinal bleeding were calculated from multivariable Cox regression analyses. DOACs were compared pairwise RESULTS: Compared with apixaban, both dabigatran and rivaroxaban were associated with a significantly increased risk of gastrointestinal bleeding with standardized 1-year risk ratios of 1.73 (95 % confidence interval [CI], 1.10-2.35) and 1.56 (95 % CI, 1.18-1.93), respectively, while no significant difference was seen in the comparison of apixaban with edoxaban 1.32 (95 % CI, 0.41-2.32). No significant differences in gastrointestinal bleeding were observed with pairwise comparisons of dabigatran, rivaroxaban and edoxaban. Finally, no significant difference in stroke risk among the four DOACs was observed.Conclusion: In AF patients with moderate or severe anaemia, apixaban was associated with a significantly lower risk of gastrointestinal bleeding than dabigatran and rivaroxaban. No significant difference in stroke risk was observed across all four available DOACs

Out-of-hospital cardiac arrest:Does rurality decrease chances of survival?

BACKGROUND: Geographical setting is seldomly taken into account when investigating out-of-hospital cardiac arrest (OHCA). It is a common notion that living in rural areas means a lower chance of fast and effective helpwhen suffering a time-critical event. This retrospective cohort study investigates this hypothesis and compares across healthcare-divided administrative regions. METHODS: We included only witnessed OHCAs to minimize the risk that outcome was predetermined by time to caller arrival and/or recognition. Arrests were divided into public and residential. Residential arrests were categorized according to population density of the area in which they occurred. We investigated incidence, EMS response time and 30-day survival according to area type and subsidiarily by healthcare-divided administrative region. RESULTS: The majority (71%) of 8,579 OHCAs were residential, and 53.2% of all arrests occurred in the most densely populated cell group amongst residential arrests. This group had a median EMS response time of six minutes, whereas the most sparsely populated group had a median of 10 minutes. Public arrests also had a median response time of six minutes. 30-day survival was highest in public arrests (38.5%, [95% CI 36.9;40.1]), and varied only slightly with no statistical significance between OHCAs in densely and sparsely populated areas from 14.8% (95% CI 14.4;15.2) and 13.4% (95% CI 12.2;14.7). CONCLUSION: Our study demonstrates that while EMS response times in Denmark are longer in the rural areas, there is no statistically significant decrease in survival compared to the most densely populated areas