BACKGROUND: COVID-19 continues to spread throughout the world. Real-time reverse transcriptase polymerase chain reaction (RT-PCR) is used to diagnose COVID-19, with its cycle threshold (Ct) value inversely related to the viral load. The association between Ct values and COVID-19 related outcomes has been studied in the hospital setting but less so in the community. We aimed to estimate the association between Ct values and the severity of community-diagnosed COVID-19 to provide evidence on the utility of Ct testing in this setting.

METHODS: This was a retrospective cohort study based on data from Israel's largest health organization. The study population included 34,658 individuals who tested positive for COVID-19 by RT-PCR and had available Ct values between June 1st and December 21st, 2020. Outcomes included COVID-19 related symptoms, hospitalization, severe disease, and death. Ct values were modelled both as discrete and continuous exposures.

RESULTS: After adjusting for known risk factors for severe COVID-19, low Ct values were associated with symptomatic disease (odds ratio [OR]: 1.51; 95% confidence interval [CI]:1.21-1.84), hospitalization (OR: 1.27; 95%CI: 1.12-1.49), severe disease (OR: 1.80; 95%CI: 1.43-2.27), and death (OR: 1.64; 95%CI: 1.06-2.59). By modelling the exposure as continuous, we noticed a dose-response relationship, with the risk gradually rising with lower Ct values.

CONCLUSIONS: This study found a significant association between low Ct values and severe COVID-19 related outcomes, with a dose-response relationship. This suggests that Ct values could be helpful in identifying high-risk patients diagnosed in the community.

BACKGROUND: COVID-19 continues to spread throughout the world. Real-time reverse transcriptase polymerase chain reaction (RT-PCR) is used to diagnose COVID-19, with its cycle threshold (Ct) value inversely related to the viral load. The association between Ct values and COVID-19 related outcomes has been studied in the hospital setting but less so in the community. We aimed to estimate the association between Ct values and the severity of community-diagnosed COVID-19 to provide evidence on the utility of Ct testing in this setting.

METHODS: This was a retrospective cohort study based on data from Israel's largest health organization. The study population included 34,658 individuals who tested positive for COVID-19 by RT-PCR and had available Ct values between June 1st and December 21st, 2020. Outcomes included COVID-19 related symptoms, hospitalization, severe disease, and death. Ct values were modelled both as discrete and continuous exposures.

RESULTS: After adjusting for known risk factors for severe COVID-19, low Ct values were associated with symptomatic disease (odds ratio [OR]: 1.51; 95% confidence interval [CI]:1.21-1.84), hospitalization (OR: 1.27; 95%CI: 1.12-1.49), severe disease (OR: 1.80; 95%CI: 1.43-2.27), and death (OR: 1.64; 95%CI: 1.06-2.59). By modelling the exposure as continuous, we noticed a dose-response relationship, with the risk gradually rising with lower Ct values.

CONCLUSIONS: This study found a significant association between low Ct values and severe COVID-19 related outcomes, with a dose-response relationship. This suggests that Ct values could be helpful in identifying high-risk patients diagnosed in the community.

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.

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: 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: 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.

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.

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.