BACKGROUND: Preapproval trials showed that messenger RNA (mRNA)-based vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) had a good safety profile, yet these trials were subject to size and patient-mix limitations. An evaluation of the safety of the BNT162b2 mRNA vaccine with respect to a broad range of potential adverse events is needed.

METHODS: We used data from the largest health care organization in Israel to evaluate the safety of the BNT162b2 mRNA vaccine. For each potential adverse event, in a population of persons with no previous diagnosis of that event, we individually matched vaccinated persons to unvaccinated persons according to sociodemographic and clinical variables. Risk ratios and risk differences at 42 days after vaccination were derived with the use of the Kaplan-Meier estimator. To place these results in context, we performed a similar analysis involving SARS-CoV-2-infected persons matched to uninfected persons. The same adverse events were studied in the vaccination and SARS-CoV-2 infection analyses.

RESULTS: In the vaccination analysis, the vaccinated and control groups each included a mean of 884,828 persons. Vaccination was most strongly associated with an elevated risk of myocarditis (risk ratio, 3.24; 95% confidence interval [CI], 1.55 to 12.44; risk difference, 2.7 events per 100,000 persons; 95% CI, 1.0 to 4.6), lymphadenopathy (risk ratio, 2.43; 95% CI, 2.05 to 2.78; risk difference, 78.4 events per 100,000 persons; 95% CI, 64.1 to 89.3), appendicitis (risk ratio, 1.40; 95% CI, 1.02 to 2.01; risk difference, 5.0 events per 100,000 persons; 95% CI, 0.3 to 9.9), and herpes zoster infection (risk ratio, 1.43; 95% CI, 1.20 to 1.73; risk difference, 15.8 events per 100,000 persons; 95% CI, 8.2 to 24.2). SARS-CoV-2 infection was associated with a substantially increased risk of myocarditis (risk ratio, 18.28; 95% CI, 3.95 to 25.12; risk difference, 11.0 events per 100,000 persons; 95% CI, 5.6 to 15.8) and of additional serious adverse events, including pericarditis, arrhythmia, deep-vein thrombosis, pulmonary embolism, myocardial infarction, intracranial hemorrhage, and thrombocytopenia.

CONCLUSIONS: In this study in a nationwide mass vaccination setting, the BNT162b2 vaccine was not associated with an elevated risk of most of the adverse events examined. The vaccine was associated with an excess risk of myocarditis (1 to 5 events per 100,000 persons). The risk of this potentially serious adverse event and of many other serious adverse events was substantially increased after SARS-CoV-2 infection. (Funded by the Ivan and Francesca Berkowitz Family Living Laboratory Collaboration at Harvard Medical School and Clalit Research Institute.).

INTRODUCTION Distal ureteral stones (DUS) are common in patients presenting to the emergency department (ED) with renal colic. The majority of DUS will pass spontaneously and therefore conservative care is common. Follow up is imperative as some of these stones might not pass and potentially lead to complications. The aim of our study was to evaluate the rate of compliance with follow up and to find predictive variables for it.

MATERIALS AND METHODS: We retrospectively surveyed the medical records of all patients who had a non-contrast computed tomography (NCCT) at our ED between 01/03/16 and 31/5/17. We included patients with a DUS smaller than 10 mm that were treated conservatively. We obtained demographic, clinical, laboratory and imaging data. Compliance to follow up was evaluated by surveying the medical records and by calling the patients. We then compared the characteristics of patients who returned for follow up to those who did not.

RESULTS: A total of 230 consecutive patients were included in our cohort: 194 (84%) patients were male and the average age was 46 y (21-82); 138 patients (60%) returned for a follow up visit while 92 patients (40%) did not. Univariate analysis revealed stone size and admission to hospital to be predictive of compliance to follow up while multivariate analysis revealed only hospital admission to be predictive of compliance.

CONCLUSIONS: Only 60% of the patients with DUS treated conservatively return for a follow up visit. Hospital admission, which likely reflects appropriate patients counseling by a urologist and adequate follow up scheduling, was found to be associated with increased compliance with follow up.

To evaluate the effectiveness of the BNT162b2 messenger RNA vaccine in pregnant women, we conducted an observational cohort study of pregnant women aged 16 years or older, with no history of SARS-CoV-2, who were vaccinated between 20 December 2020 and 3 June 2021. A total of 10,861 vaccinated pregnant women were matched to 10,861 unvaccinated pregnant controls using demographic and clinical characteristics. Study outcomes included documented infection with SARS-CoV-2, symptomatic COVID-19, COVID-19-related hospitalization, severe illness and death. Estimated vaccine effectiveness from 7 through to 56 d after the second dose was 96% (95% confidence interval 89-100%) for any documented infection, 97% (91-100%) for infections with documented symptoms and 89% (43-100%) for COVID-19-related hospitalization. Only one event of severe illness was observed in the unvaccinated group and no deaths were observed in either group. In summary, the BNT162b2 mRNA vaccine was estimated to have high vaccine effectiveness in pregnant women, which is similar to the effectiveness estimated in the general population.

BACKGROUND: Preapproval trials showed that messenger RNA (mRNA)-based vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) had a good safety profile, yet these trials were subject to size and patient-mix limitations. An evaluation of the safety of the BNT162b2 mRNA vaccine with respect to a broad range of potential adverse events is needed.

METHODS: We used data from the largest health care organization in Israel to evaluate the safety of the BNT162b2 mRNA vaccine. For each potential adverse event, in a population of persons with no previous diagnosis of that event, we individually matched vaccinated persons to unvaccinated persons according to sociodemographic and clinical variables. Risk ratios and risk differences at 42 days after vaccination were derived with the use of the Kaplan-Meier estimator. To place these results in context, we performed a similar analysis involving SARS-CoV-2-infected persons matched to uninfected persons. The same adverse events were studied in the vaccination and SARS-CoV-2 infection analyses.

RESULTS: In the vaccination analysis, the vaccinated and control groups each included a mean of 884,828 persons. Vaccination was most strongly associated with an elevated risk of myocarditis (risk ratio, 3.24; 95% confidence interval [CI], 1.55 to 12.44; risk difference, 2.7 events per 100,000 persons; 95% CI, 1.0 to 4.6), lymphadenopathy (risk ratio, 2.43; 95% CI, 2.05 to 2.78; risk difference, 78.4 events per 100,000 persons; 95% CI, 64.1 to 89.3), appendicitis (risk ratio, 1.40; 95% CI, 1.02 to 2.01; risk difference, 5.0 events per 100,000 persons; 95% CI, 0.3 to 9.9), and herpes zoster infection (risk ratio, 1.43; 95% CI, 1.20 to 1.73; risk difference, 15.8 events per 100,000 persons; 95% CI, 8.2 to 24.2). SARS-CoV-2 infection was associated with a substantially increased risk of myocarditis (risk ratio, 18.28; 95% CI, 3.95 to 25.12; risk difference, 11.0 events per 100,000 persons; 95% CI, 5.6 to 15.8) and of additional serious adverse events, including pericarditis, arrhythmia, deep-vein thrombosis, pulmonary embolism, myocardial infarction, intracranial hemorrhage, and thrombocytopenia.

CONCLUSIONS: In this study in a nationwide mass vaccination setting, the BNT162b2 vaccine was not associated with an elevated risk of most of the adverse events examined. The vaccine was associated with an excess risk of myocarditis (1 to 5 events per 100,000 persons). The risk of this potentially serious adverse event and of many other serious adverse events was substantially increased after SARS-CoV-2 infection. (Funded by the Ivan and Francesca Berkowitz Family Living Laboratory Collaboration at Harvard Medical School and Clalit Research Institute.).

Early risk stratification is essential for determining the appropriate therapeutic management approach of pulmonary embolism (PE). This study aimed to evaluate the prognostic value of the neutrophil-to-lymphocyte ratio (NLR) in patients hospitalized with acute pulmonary embolism by investigating its association with mortality in a large-scale population diagnosed and hospitalized with acute PE. We retrieved all consecutive patients hospitalized in an internal medicine department or an intensive care unit in a tertiary medical center from December 2007 to April 2021 with a discharge diagnosis of pulmonary embolism. A total of 2072 patients were included. Patients with above-median NLR (i.e., 5.12) had a higher 30-day mortality risk (adjusted odds ratio (aOR), 2.82; 95% confidence interval (CI) 2.14-3.70) and higher one-year mortality risk (aOR, 2.51; 95% CI 2.04-3.08). Similar trends were demonstrated in a sub-analysis of patients without cancer and hemodynamically stable (i.e., systolic blood pressure over 90 mmHg). Furthermore, the median hospital length of stay in patients with an elevated NLR was higher, and so was the in-hospital mortality rate. Elevated NLR in acute PE is associated with a worse short-term and long-term prognosis and with a longer duration of hospitalization.

BACKGROUND: Reports have suggested an association between the development of myocarditis and the receipt of messenger RNA (mRNA) vaccines against coronavirus disease 2019 (Covid-19), but the frequency and severity of myocarditis after vaccination have not been extensively explored.

METHODS: We searched the database of Clalit Health Services, the largest health care organization (HCO) in Israel, for diagnoses of myocarditis in patients who had received at least one dose of the BNT162b2 mRNA vaccine (Pfizer-BioNTech). The diagnosis of myocarditis was adjudicated by cardiologists using the case definition used by the Centers for Disease Control and Prevention. We abstracted the presentation, clinical course, and outcome from the patient's electronic health record. We performed a Kaplan-Meier analysis of the incidence of myocarditis up to 42 days after the first vaccine dose.

RESULTS: Among more than 2.5 million vaccinated HCO members who were 16 years of age or older, 54 cases met the criteria for myocarditis. The estimated incidence per 100,000 persons who had received at least one dose of vaccine was 2.13 cases (95% confidence interval [CI], 1.56 to 2.70). The highest incidence of myocarditis (10.69 cases per 100,000 persons; 95% CI, 6.93 to 14.46) was reported in male patients between the ages of 16 and 29 years. A total of 76% of cases of myocarditis were described as mild and 22% as intermediate; 1 case was associated with cardiogenic shock. After a median follow-up of 83 days after the onset of myocarditis, 1 patient had been readmitted to the hospital, and 1 had died of an unknown cause after discharge. Of 14 patients who had left ventricular dysfunction on echocardiography during admission, 10 still had such dysfunction at the time of hospital discharge. Of these patients, 5 underwent subsequent testing that revealed normal heart function.

CONCLUSIONS: Among patients in a large Israeli health care system who had received at least one dose of the BNT162b2 mRNA vaccine, the estimated incidence of myocarditis was 2.13 cases per 100,000 persons; the highest incidence was among male patients between the ages of 16 and 29 years. Most cases of myocarditis were mild or moderate in severity. (Funded by the Ivan and Francesca Berkowitz Family Living Laboratory Collaboration at Harvard Medical School and Clalit Research Institute.).

Evidence regarding the effectiveness of covid-19 vaccine in patients with impaired immunity, is limited. Initial observations suggest a lower humoral response in these patients. We evaluated the relative effectiveness of the mRNA BNT162b2 vaccine in patients with hematological neoplasms compared to matched controls. Data on patients with hematological neoplasms after two vaccine doses were extracted and matched 1:1 with vaccinated controls. Subpopulation analyses focused on patients receiving therapy for the hematological neoplasm, patients without treatment who are only followed, and recipients of specific treatments. The analysis focused on covid-19 outcomes from day 7 through 43 following the second vaccine dose: Documented covid-19 infection by PCR; Symptomatic infection; Hospitalizations; Severe covid-19 disease and covid-19-related death. Of a population of 4.7 million insured people, 32,516 patients with hematological neoplasms were identified, of whom 5,017 were receiving therapy for an active disease. Vaccinated patients with hematological neoplasms, compared with vaccinated matched controls, had an increased risk of documented infections (RR 1.60, 95% confidence interval [CI] 1.12-2.37), symptomatic covid-19 (RR 1.72, 95% CI 1.05-2.85), covid-19 related hospitalizations (RR 3.13, 95% CI 1.68-7.08), severe covid-19 (RR 2.27, 95% CI 1.18-5.19) and covid-19 related death (RR 1.66, 95% CI 0.72-4.47). Limiting the analysis to patients on hematological treatments showed a higher increased risk. This analysis shows that vaccinated patients with hematological neoplasms, in particular patients on treatment, suffer from covid-19 outcomes more than vaccinated individuals with intact immune system. Ways to enhance covid-19 immunity in this patient population, such as additional doses, should be explored.

BACKGROUND: Many countries are experiencing a resurgence of COVID-19, driven predominantly by the delta (B.1.617.2) variant of SARS-CoV-2. In response, these countries are considering the administration of a third dose of mRNA COVID-19 vaccine as a booster dose to address potential waning immunity over time and reduced effectiveness against the delta variant. We aimed to use the data repositories of Israel's largest health-care organisation to evaluate the effectiveness of a third dose of the BNT162b2 mRNA vaccine for preventing severe COVID-19 outcomes.

METHODS: Using data from Clalit Health Services, which provides mandatory health-care coverage for over half of the Israeli population, individuals receiving a third vaccine dose between July 30, 2020, and Sept 23, 2021, were matched (1:1) to demographically and clinically similar controls who did not receive a third dose. Eligible participants had received the second vaccine dose at least 5 months before the recruitment date, had no previous documented SARS-CoV-2 infection, and had no contact with the health-care system in the 3 days before recruitment. Individuals who are health-care workers, live in long-term care facilities, or are medically confined to their homes were excluded. Primary outcomes were COVID-19-related admission to hospital, severe disease, and COVID-19-related death. The third dose effectiveness for each outcome was estimated as 1 - risk ratio using the Kaplan-Meier estimator.

FINDINGS: 1 158 269 individuals were eligible to be included in the third dose group. Following matching, the third dose and control groups each included 728 321 individuals. Participants had a median age of 52 years (IQR 37-68) and 51% were female. The median follow-up time was 13 days (IQR 6-21) in both groups. Vaccine effectiveness evaluated at least 7 days after receipt of the third dose, compared with receiving only two doses at least 5 months ago, was estimated to be 93% (231 events for two doses vs 29 events for three doses; 95% CI 88-97) for admission to hospital, 92% (157 vs 17 events; 82-97) for severe disease, and 81% (44 vs seven events; 59-97) for COVID-19-related death.

INTERPRETATION: Our findings suggest that a third dose of the BNT162b2 mRNA vaccine is effective in protecting individuals against severe COVID-19-related outcomes, compared with receiving only two doses at least 5 months ago.

FUNDING: The Ivan and Francesca Berkowitz Family Living Laboratory Collaboration at Harvard Medical School and Clalit Research Institute.