BACKGROUND: Emerging data suggest increased arterial thrombosis risk in the months preceding a cancer diagnosis.

OBJECTIVES: To assess whether patients without documented vascular risk factors or pre-existing cardiovascular disease have a higher relative risk of cancer 12 months after arterial thrombotic events (ATE), compared to unselected patients.

PATIENTS/METHODS: A population-based cohort study of Clalit Health Services (CHS) database included CHS members ≥25 years without prior cancer or ATE (n = 2 804 584). An iterative matching process selected 10 potential controls chronologically for each consecutive exposed, age- and sex-matched (actual controls drawn 1:1 from a lot). Study exposure, ATE, was defined as ischemic stroke, transient ischemic attack, myocardial infarction or systemic arterial thromboembolism during hospitalization. The outcome was newly-diagnosed cancer within 12 months, based on Israeli national cancer registry. Cox proportional hazards multivariate regression calculated hazard ratio (HR) for outcomes, adjusted for cancer risk factors. Analysis also performed for three subgroups: age ≤50 years; no cardiovascular risk factors; no prior cardiovascular disease.

RESULTS: The full ATE and matched control cohorts included 43 108 patients. The 12-month cumulative incidence of cancer (95% confidence interval) was 0.020 (0.019-0.022) in the ATE cohort and 0.012 (0.011-0.013) in controls, corresponding to an adjusted HR of 1.665 (1.489-1.862). The relative risk of cancer was high in all subgroups up to a HR of 3.754 (1.912-7.372) in patients without cardiovascular risk factors.

CONCLUSION: There is an increased risk of previously undiagnosed cancer at 12 months after ATE, especially in patients without documented vascular risk factors or pre-existent cardiovascular disease.

BACKGROUND: Most studies estimate hepatitis C virus (HCV) disease prevalence from convenience samples. Consequently, screening policies may not include those at the highest risk for a new diagnosis.

METHODS: Clalit Health Services members aged 25-74 as of 31 December 2009 were included in the study. Rates of testing and new diagnoses of HCV were calculated, and potential risk groups were examined.

RESULTS: Of the 2 029 501 included members, those aged 45-54 and immigrants had lower rates of testing (12.5% and 15.6%, respectively), higher rates of testing positive (0.8% and 1.1%, respectively), as well as the highest rates of testing positive among tested (6.1% and 6.9%, respectively).

DISCUSSION: In this population-level study, groups more likely to test positive for HCV also had lower rates of testing. Policy makers and clinicians worldwide should consider creating screening policies using on population-based data to maximize the ability to detect and treat incident cases.

Heart failure (HF) prevalence is increasing worldwide and is associated with significant morbidity and mortality. Guidelines emphasize prevention in those at-risk, but HF-specific risk prediction equations developed in United States population-based cohorts lack external validation in large, real-world datasets outside of the United States. The purpose of this study was to assess the model performance of the pooled cohort equations to prevent HF (PCP-HF) within a contemporary electronic health record for 5- and 10-year risk. Using a retrospective cohort study design of Israeli residents between 2008 and 2018 with continuous membership until end of follow-up, HF, or death, we quantified 5- and 10-year estimated risks of HF using the PCP-HF equations, which integrate demographics (age, gender, and race) and risk factors (body mass index, systolic blood pressure, glucose, medication use for hypertension or diabetes, and smoking status). Of 1,394,411 patients included, 56% were women with mean age of 49.6 (SD 13.2) years. Incident HF occurred in 1.2% and 4.5% of participants over 5 and 10 years of follow-up. The PCP-HF model had excellent discrimination for 5- and 10-year predictions of incident HF (C Statistic 0.82 [0.82 to 0.82] and 0.84 [0.84 to 0.84]), respectively. In conclusion, HF-specific risk equations (PCP-HF) accurately predict the risk of incident HF in ambulatory and hospitalized patients using routinely available clinical data.

Heart failure (HF) prevalence is increasing worldwide and is associated with significant morbidity and mortality. Guidelines emphasize prevention in those at-risk, but HF-specific risk prediction equations developed in United States population-based cohorts lack external validation in large, real-world datasets outside of the United States. The purpose of this study was to assess the model performance of the pooled cohort equations to prevent HF (PCP-HF) within a contemporary electronic health record for 5- and 10-year risk. Using a retrospective cohort study design of Israeli residents between 2008 and 2018 with continuous membership until end of follow-up, HF, or death, we quantified 5- and 10-year estimated risks of HF using the PCP-HF equations, which integrate demographics (age, gender, and race) and risk factors (body mass index, systolic blood pressure, glucose, medication use for hypertension or diabetes, and smoking status). Of 1,394,411 patients included, 56% were women with mean age of 49.6 (SD 13.2) years. Incident HF occurred in 1.2% and 4.5% of participants over 5 and 10 years of follow-up. The PCP-HF model had excellent discrimination for 5- and 10-year predictions of incident HF (C Statistic 0.82 [0.82 to 0.82] and 0.84 [0.84 to 0.84]), respectively. In conclusion, HF-specific risk equations (PCP-HF) accurately predict the risk of incident HF in ambulatory and hospitalized patients using routinely available clinical data.

BACKGROUND: Methodologically rigorous studies on Covid-19 vaccine effectiveness (VE) in preventing SARS-CoV-2 infection are critically needed to inform national and global policy on Covid-19 vaccine use. In Israel, healthcare personnel (HCP) were initially prioritized for Covid-19 vaccination, creating an ideal setting to evaluate early real-world VE in a closely monitored population.

METHODS: We conducted a prospective study among HCP in 6 hospitals to estimate the effectiveness of the BNT162b2 mRNA Covid-19 vaccine in preventing SARS-CoV-2 infection. Participants filled out weekly symptom questionnaires, provided weekly nasal specimens, and three serology samples - at enrollment, 30 days and 90 days. We estimated VE against PCR-confirmed SARS-CoV-2 infection using the Cox Proportional Hazards model and against a combined PCR/serology endpoint using Fisher's exact test.

RESULTS: Of the 1567 HCP enrolled between December 27, 2020 and February 15, 2021, 1250 previously uninfected participants were included in the primary analysis; 998 (79.8%) were vaccinated with their first dose prior to or at enrollment, all with Pfizer BNT162b2 mRNA vaccine. There were four PCR-positive events among vaccinated participants, and nine among unvaccinated participants. Adjusted two-dose VE against any PCR-confirmed infection was 94.5% (95% CI: 82.6%-98.2%); adjusted two-dose VE against a combined endpoint of PCR and seroconversion for a 60-day follow-up period was 94.5% (95% CI: 63.0%-99.0%). Five PCR-positive samples from study participants were sequenced; all were alpha variant.

CONCLUSIONS: Our prospective VE study of HCP in Israel with rigorous weekly surveillance found very high VE for two doses of Pfizer BNT162b2 mRNA vaccine against SARS-CoV-2 infection in recently vaccinated HCP during a period of predominant alpha variant circulation.

FUNDING: Clalit Health Services.

BACKGROUND: Methodologically rigorous studies on Covid-19 vaccine effectiveness (VE) in preventing SARS-CoV-2 infection are critically needed to inform national and global policy on Covid-19 vaccine use. In Israel, healthcare personnel (HCP) were initially prioritized for Covid-19 vaccination, creating an ideal setting to evaluate early real-world VE in a closely monitored population.

METHODS: We conducted a prospective study among HCP in 6 hospitals to estimate the effectiveness of the BNT162b2 mRNA Covid-19 vaccine in preventing SARS-CoV-2 infection. Participants filled out weekly symptom questionnaires, provided weekly nasal specimens, and three serology samples - at enrollment, 30 days and 90 days. We estimated VE against PCR-confirmed SARS-CoV-2 infection using the Cox Proportional Hazards model and against a combined PCR/serology endpoint using Fisher's exact test.

RESULTS: Of the 1567 HCP enrolled between December 27, 2020 and February 15, 2021, 1250 previously uninfected participants were included in the primary analysis; 998 (79.8%) were vaccinated with their first dose prior to or at enrollment, all with Pfizer BNT162b2 mRNA vaccine. There were four PCR-positive events among vaccinated participants, and nine among unvaccinated participants. Adjusted two-dose VE against any PCR-confirmed infection was 94.5% (95% CI: 82.6%-98.2%); adjusted two-dose VE against a combined endpoint of PCR and seroconversion for a 60-day follow-up period was 94.5% (95% CI: 63.0%-99.0%). Five PCR-positive samples from study participants were sequenced; all were alpha variant.

CONCLUSIONS: Our prospective VE study of HCP in Israel with rigorous weekly surveillance found very high VE for two doses of Pfizer BNT162b2 mRNA vaccine against SARS-CoV-2 infection in recently vaccinated HCP during a period of predominant alpha variant circulation.

FUNDING: Clalit Health Services.

Children unvaccinated against SARS-CoV-2 may still benefit through protection from vaccinated contacts. We estimated the protection provided to children through parental vaccination with the BNT162b2 vaccine. We studied households without prior infection, consisting of two parents and unvaccinated children, estimating the effect of parental vaccination on the risk of infection for unvaccinated children. We studied two periods separately- an early period (January 17, 2021 - March 28, 2021, Alpha variant, two doses vs. no vaccination) and a late period (July 11, 2021 - September 30, 2021, Delta variant, booster dose vs. two-vaccine doses). We found that having a single vaccinated parent was associated with a 26.0% and 20.8% decreased risk, and having two vaccinated parents was associated with a 71.7% and 58.1% decreased risk, in the early and late periods, respectively. To conclude, parental vaccination confers substantial protection for unvaccinated children in the household.

Children unvaccinated against SARS-CoV-2 may still benefit through protection from vaccinated contacts. We estimated the protection provided to children through parental vaccination with the BNT162b2 vaccine. We studied households without prior infection, consisting of two parents and unvaccinated children, estimating the effect of parental vaccination on the risk of infection for unvaccinated children. We studied two periods separately- an early period (January 17, 2021 - March 28, 2021, Alpha variant, two doses vs. no vaccination) and a late period (July 11, 2021 - September 30, 2021, Delta variant, booster dose vs. two-vaccine doses). We found that having a single vaccinated parent was associated with a 26.0% and 20.8% decreased risk, and having two vaccinated parents was associated with a 71.7% and 58.1% decreased risk, in the early and late periods, respectively. To conclude, parental vaccination confers substantial protection for unvaccinated children in the household.

Objective: To evaluate whether a woman's age at first birth is associated with cardiovascular risk and metabolic health outcomes (cardiometabolic outcomes) by age 45.Methods: This is a retrospective, population-based cohort study that uses electronic health record data from the largest health fund in Israel. Women aged 34-39 at baseline (2004-2006) free of chronic diseases were identified as nulliparous at baseline and were followed up to 10 years (through 2016). The cohort was divided into three groups based on their age at first birth: younger parturients (ages 35-39), older parturients (ages 40-44), and never had children. The percentage of adverse pregnancy events and cardiometabolic outcomes at age 45 were compared across these three groups as well as to women in the general population. Cardiovascular risk and metabolic health outcomes were defined as: Type 2 diabetes, obesity, hypertension, cardiovascular disease, and Framingham risk score.Methods and results: Out of a group of 126,121 women aged 34-39 at baseline, 9979 were nulliparous and free of comorbidities. Over the course of the follow-up, there were 952 younger parturients and 673 older parturients who had their first birth, and 8354 women who remained persistent nulliparous. While older parturients had more adverse pregnancy events, there was no difference in rates of cardiometabolic outcomes between the two parturient groups, and they both had lower rates than the persistent nulliparous and the general population.Conclusions: Parturients free of major chronic diseases who give birth at a later age do not have increased cardiometabolic outcomes in midlife as compared to a general population of women in a large retrospective cohort. Our results may support clinicians when counseling healthy women who are seeking advice regarding delaying their first pregnancy without a tradeoff on health outcomes.

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.