Pfizer COVID19 vaccine is not associated with acute cardiovascular events excluding myocarditis- a national self-controlled case series study.

BACKGROUND: Despite publications assuring no increased risk for acute cardiovascular events (excluding myocarditis) and sudden death following administration of COVID19 vaccines, these issues still stir much public ado. We assessed the risk for acute cardiovascular events that require hospitalization (excluding myocarditis) and for mortality in the short-term following administration of the second dose of the Pfizer COVID19 vaccine in Israel. METHODS: Using a self-controlled case series (SCCS) study design and national databases, all second-dose vaccinees, who had not been diagnosed with COVID19 and who had an acute cardiovascular event (acute myocardial infarction/acute stroke/acute thromboembolic event) that required hospitalization in the 60 days following vaccine administration between Jan 11th, 2021 and Oct 31st 2021, were included. A similar analysis was carried out for mortality. The first 30 days following vaccination were defined as risk period while the next 30 days were defined as control period. The probability for an event between these periods was compared using a conditional logistic regression model, accounting for sex, age group, background morbidity and seasonal risk. RESULTS: Out of 5,700,112  second dose vaccinees, 4,163 had an acute cardiovascular event in the 60 days following vaccine administration. Following exclusion of 106 due to technical considerations, 1,979 events occurred during the risk period and 2,078 during the control period: Odds ratio, OR = 0.95, 95% confidence interval, CI 0.90-1.01, p = 0.12. Adjusted OR was similar (OR = 0.88, 95%CI 0.72-1.08). Stratifying by age showed no increased risk in any age group. Mortality assessment indicated low number of events in both periods. These results were consistent in sensitivity analyses. CONCLUSIONS: There was no increased risk for acute cardiovascular events (excluding myocarditis) in the risk period compared to the control period following administration of the second dose of Pfizer COVID19 vaccine. Mortality data raised no concerns either, but may have been biased.

Risk Factors for Multiple Infections with Salmonella, Shigella, and Campylobacter in Single Individuals Identified in Israel between 1999 and 2020: A Case-Case Control Study.

BACKGROUND: Salmonella, Shigella, and Campylobacter are highly prevalent among children. Reports on risk factors of patients infected with all three pathogens, not simultaneously, are scarce. OBJECTIVES: To identify risk factors for multiple infection with Salmonella, Shigella, and Campylobacter in the same child. METHODS: Using the Israel Sentinel Laboratory-Based Surveillance Network, we conducted a retrospective observational case-case-control study among children aged 0-9 years. A case was defined as a child infected with Salmonella, Shigella, and Campylobacter at different occasions between January 1999 and December 2020. A control was defined as a child infected with a single pathogen once, during the same period. Logistic regression models were applied to determine the association between multiple infections and demographic characteristics. RESULTS: We identified 109 cases (0.1%) infected with Salmonella, Shigella, and Campylobacter, and 86,511 controls (99.9%) infected with only one bacteria type. In a multivariable analysis, we showed that being Jewish (odds ratio [OR] 2.4, 95% confidence interval [95%CI] 1.3-4.4), having residency in Jerusalem (OR 3.2, 95%CI 1.3-7.7), or in the southern district (OR 3.7, 95%CI 1.5-8.8) were independent risk factors for multiple infection. CONCLUSIONS: Although very rare, non-simultaneous infection with multiple bacteria does occur in Israel. National and local authorities should promote programs to encourage proper hygiene practices, which are culture-adjusted.

Quantifying the Population-Level Effect of the COVID-19 Mass Vaccination Campaign in Israel: A Modeling Study.

Background: Estimating real-world vaccine effectiveness is challenging as a variety of population factors can impact vaccine effectiveness. We aimed to assess the population-level reduction in cumulative severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) cases, hospitalizations, and mortality due to the BNT162b2 mRNA coronavirus disease 2019 (COVID-19) vaccination campaign in Israel during January-February 2021. Methods: A susceptible-infected-recovered/removed (SIR) model and a Dynamic Survival Analysis (DSA) statistical approach were used. Daily counts of individuals who tested positive and of vaccine doses administered, obtained from the Israeli Ministry of Health, were used to calibrate the model. The model was parameterized using values derived from a previous phase of the pandemic during which similar lockdown and other preventive measures were implemented in order to take into account the effect of these prevention measures on COVID-19 spread. Results: Our model predicted for the total population a reduction of 648 585 SARS-CoV-2 cases (75% confidence interval [CI], 25 877-1 396 963) during the first 2 months of the vaccination campaign. The number of averted hospitalizations for moderate to severe conditions was 16 101 (75% CI, 2010-33 035), and reduction of death was estimated at 5123 (75% CI, 388-10 815) fatalities. Among children aged 0-19 years, we estimated a reduction of 163 436 (75% CI, 0-433 233) SARS-CoV-2 cases, which we consider to be an indirect effect of the vaccine. Conclusions: Our results suggest that the rapid vaccination campaign prevented hundreds of thousands of new cases as well as thousands of hospitalizations and fatalities and has probably averted a major health care crisis.

Reopening Schools and the Dynamics of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Infections in Israel: A Nationwide Study.

BACKGROUND: Benefits of school reopening must be weighed against the morbidity and mortality risks and the impact of enhancing spread of coronavirus disease 2019 (COVID-19). We investigated the effects of school reopening and easing of social-distancing restrictions on dynamics of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections in Israel between March and July 2020. METHODS: We examined the nationwide age-wise weekly incidence, prevalence, SARS-CoV-2 polymerase chain reaction tests, their positivity, COVID-19 hospitalizations, and associated mortality. Temporal differences in these parameters following school reopening, school ending, and following easing of restrictions such as permission of large-scale gatherings were examined. RESULTS: Incidence of SARS-CoV-2 infections gradually increased following school reopening in all age groups, with a significantly higher increase in adults than children. Higher rate ratios (RRs) of sample positivity rates 21-27 days following school reopening relative to positivity rates prior to openings were found for the age groups 40-59 (RR, 4.72; 95% CI, 3.26-6.83) and 20-39 (RR, 3.37 [2.51-4.53]) years, but not for children aged 0-9 (RR, 1.46 [.85-2.51]) and 10-19 (RR, .93 [.65-1.34]) years. No increase was observed in COVID-19-associated hospitalizations and deaths following school reopening. In contrast, permission of large-scale gatherings was accompanied by increases in incidence and positivity rates of samples for all age groups, and increased hospitalizations and mortality. CONCLUSIONS: This analysis does not support a major role of school reopening in the resurgence of COVID-19 in Israel. Easing restrictions on large-scale gatherings was the major influence on this resurgence.

Trends in Bariatric Surgery: a 5-Year Analysis of the Israel National Bariatric Surgery Registry.

BACKGROUND: The worldwide prevalence of obesity nearly tripled between 1975 and 2016. There are limited data quantifying national trends. The aim of this study is to evaluate and summarize current trends in bariatric surgery in Israel. METHODS: Data for all bariatric surgeries (BS) performed between January 2014 and December 2018 was collected from the Israel National Bariatric Surgery Registry (INBSR) and analyzed. RESULTS: During the study period, 42,296 BS were included in the INBSR. Females accounted for 68% and the mean age and body mass index were 41.6 ± 12.6 years and 42.0 ± 5.4 kg/m2, respectively. Most of the patients were Jewish, but there was a significant rise in number of Arabs undergoing BS during the study period. There was a gradual decline in the annual numbers of BS, except for a small rise in 2015. There was a significant rise in the rate of One Anastomosis-Mini Gastric Bypass (OAGB-MGB), from 0.1% in 2014 to 46.1% in 2018, making it the most prevalent BS in that year. Laparoscopic sleeve gastrectomy (SG) surgeries decreased steadily, from 80% in 2014 to 37% in 2018. The annual rate of Roux-en-Y gastric bypass (RYGB) remained essentially constant at 10%. The annual rates of gastric banding decreased sharply and the annual rates of duodenal switch, single anastomosis duodenal switch and biliopancreatic diversion were negligible. Bariatric surgery was distributed evenly between private (50.4%) and public (49.6%) hospitals. CONCLUSIONS: The numbers of BS are decreasing in Israel. There is a gradual but noticeable shift from SG to OAGB-MGB.

Risk of second primary neoplasm and mortality in childhood cancer survivors based on a national registry database.

OBJECTIVE: Although overall childhood cancer survival has improved, survivors may still have an elevated risk for second primary neoplasm (SPN) and excess mortality. The aim of the current study was to estimate the risks for SPN and mortality in childhood cancer survivors in Israel as compared to the general population. METHODS: All children aged 0-19 diagnosed with primary neoplasm between 1980-2007 who survived at least 5 years following diagnosis were included in the study. Follow-up continued until December 31st, 2013, or diagnosis of SPN, or death due to any cause (the earliest of these events). Standardized incidence ratios (SIRs) and standardized mortality ratios (SMRs) were calculated. Cox proportional hazards regression was employed to assess predictors of SPN and mortality. RESULTS: The cohort consisted of 6637 childhood cancer survivors. A total of 244 all-site SPN cases were observed. Compared to the general population, the risks for SPN and for mortality were significantly increased (SIR = 5.48; 95%CI: 4.82-6.22 and SMR = 13.99; 95%CI = 12.54-15.56, respectively). Factors predicting SPN were sex (female), older age at first diagnosis, and initial cancer diagnosis (lymphomas). Factors predicting mortality were older age at first diagnosis, initial cancer diagnosis (myeloproliferative diseases) and earlier years, according to calendar period of initial diagnosis. CONCLUSIONS: Although 5-year childhood cancer survival is high, survivors are at elevated risk for SPN and mortality, and the risks are associated with baseline characteristics of the patients. The increased risks should be considered when planning treatment, follow-up and surveillance of the survivors.

Development and validation of a tool to evaluate Inpatient Beliefs, Expectations and Attitudes toward Reflexology (IBEAR-16).

BACKGROUND: The integration of manual therapies, including reflexology, into conventional care settings is growing extensively. Patients' beliefs, attitudes and expectations toward these therapies interact with their outcomes, but currently there are no validated tools to evaluate these factors. We aimed to design and to validate such a tool specifically targeted into reflexology. METHODS: Following input of a multidisciplinary team of experts, the self-administered Inpatient Beliefs, Expectations and Attitudes toward Reflexology (IBEAR) questionnaire was constructed, containing 25 items, 8 referring to demographics and 17 specifically addressing reflexology. Cronbach's alpha was computed to evaluate the questionnaire's internal reliability, and factor analysis was used for further validation (232 patients). Pearson coefficient and Kappa tests were used to test and retest (within 48 hours) the questionnaire on a group of 199 patients, to assure clarity and reliability. RESULTS: For the 232 questionnaires collected, the computed Cronbach's alpha coefficient was 0.716 (acceptable reliability). Factor analysis pointed to two content areas separated into four items addressing attitudes and expectations and five items focusing on beliefs and attitudes. In the test-retest stage, 199 participants filled in the questionnaire for a second time. The Pearson coefficient for all questions ranged between 0.73 and 0.94 (good to excellent correlation) and Kappa scores ranged between 0.66 and 1.0 (moderate to high reliability). Consequently, one of the questions was removed from the IBEAR. CONCLUSIONS: The present study provides evidence that the proposed IBEAR questionnaire with 16 items is a valid and reliable tool for evaluation of inpatients' beliefs, expectations and attitudes toward reflexology.

Primary Peritoneal Serous Carcinoma in Men: A Rare and Non-BRCA-associated Entity.

BACKGROUND: Primary peritoneal serous carcinoma (PPSC) is a rare neoplasm. The paucity of reported cases among men may provide insight to the cell of origin of PPSC. MATERIALS AND METHODS: A search for the ICD 0-3 code of PPSC (C48.2) in the following datasets: the Israeli National Cancer registry (INCR), the Surveillance, Epidemiology, and End Results (SEER) database in the USA, Israeli male BRCA carriers, male high-risk and BRCA carriers in a USA study, and the Italian Study on Male Breast Cancer (MBC) were performed. RESULTS: In the INCR dataset, 220 entries for C48.2 code were noted, with only one male (male:female ratio=0.0045). In the SEER dataset for histology codes of papillary/serous/ adenocarcinoma, 2,673 cases were recorded, with five males (male:female ratio=0.0018). None of the recorded US or Italian male BRCA carriers or MBC, or Israeli male BRCA carriers was diagnosed with PPSC. CONCLUSION: PPSC is a rare neoplasm, seemingly not associated with BRCA mutations in men, and fallopian tube epithelial cell implants may contribute to its development.

Time-Dependent Risk of Cancer After a Diabetes Diagnosis in a Cohort of 2.3 Million Adults.

Using a time-dependent approach, we investigated all-site and site-specific cancer incidence in a large population stratified by diabetes status. The study analyzed a closed cohort comprised of Israelis aged 21-89 years, enrolled in a health fund, and followed from 2002 to 2012. Adjusting for age, ethnicity, and socioeconomic status, we calculated hazard ratios for cancer incidence using Cox regression separately for participants with prevalent and incident diabetes; the latter was further divided by time since diabetes diagnosis. Of the 2,186,196 individuals included in the analysis, 159,104 were classified as having prevalent diabetes, 408,243 as having incident diabetes, and 1,618,849 as free of diabetes. In both men and women, diabetes posed an increased risk of cancers of the liver, pancreas, gallbladder, endometrium, stomach, kidney, brain (benign), brain (malignant), colon/rectum, lung (all, adenocarcinoma, and squamous cell carcinoma), ovary, and bladder, as well as leukemia, multiple myeloma, non-Hodgkin lymphoma, and breast cancer in postmenopausal women. No excess risk was observed for breast cancer in premenopausal women or for thyroid cancer. Diabetes was associated with a reduced risk of prostate cancer. Hazard ratios for all-site and site-specific cancers were particularly elevated during the first year following diabetes diagnosis. The findings of this large study with a time-dependent approach are consistent with those of previous studies that have observed associations between diabetes and cancer incidence.

Muscle function and fat content in relation to sarcopenia, obesity and frailty of old age--An overview.

BACKGROUND AND AIM: In western countries, the proportion of people over age 60 is increasing faster than any other group. This is linked to higher rates of obesity. Older age, co-morbidities and obesity are all associated with frailty syndrome. In the core of both frailty and sarcopenia there are dysfunction and deterioration of the muscle and the fat tissues. This overview interlinks the phenotypes presented in older adults such as sarcopenia and frailty-alone and with relation to obesity, muscle function and fat tissue accumulation. RECENT FINDINGS: Observational studies have well described the loss of muscle mass and strength through the years of adult life, both components of frailty and sarcopenia. They have shown that these changes are associated with dysmetabolism and functional deterioration, independent of common explanatory variables. In the metabolic mechanism core of this link, insulin resistance and higher ectopic fat accumulation may play a role. Basic experiments have partially validated this hypothesis. Whether there is a synergistic effect of obesity and frailty phenotype on morbidity risk is still questionable and currently under investigation; however, few cohort studies have shown that the frail-obese or sarcopenic-obese group have higher probability for metabolic complications. SUMMARY: Muscle mass loss and fat accumulation in the muscle in the elderly, with or without the presence of obesity, may explain some of the functional and metabolic defects shown in the frail, sarcopenic population.

[The relationship between passive smoking, breast cancer risk and n-acetyltransferase 2 (NAT2)].

Invasive breast cancer is a leading cause of morbidity and mortality as well as the most common malignancy among Israeli women. Over 3,800 Israeli women are diagnosed with invasive breast cancer every year and around 3400 women are diagnosed with breast carcinoma in-situ. Although smoking, either active or passive, is a controversial risk factor for breast cancer, cigarette smoking involves exposure to substrates of the NAT2 gene. The NAT2 genotype may modify the risk of cancer by activating or detoxifying heterocyclic and aromatic amines. Identification of a potential, modifiable risk factor for common and serious disease is very important for prevention and identification of high risk groups. This literature review aims to describe published studies and increase attention to measures of exposure to tobacco smoke, as well as to aspects of the NAT2 genotype that may modify the association between passive smoking and breast cancer risk. The results suggest that the NAT2 status has a differential effect on the association of active and passive smoking with breast cancer and demonstrates the need to consider possible different mechanisms associated with exposure to main and side-stream tobacco smoke. However, methodological limitations, such as small sample size, and varying definitions of smoking, are likely to have contributed to the inconsistent findings.

Diabetes, glucose control, glucose lowering medications, and cancer risk: a 10-year population-based historical cohort.

BACKGROUND: Both diabetes and glucose-lowering medications have been associated with an increased risk of cancer incidence. This study will compare cancer incidence rates in individuals with and without diabetes; and will investigate, in individuals with diabetes, an association between glucose control and cancer incidence; and between the use of specific glucose-lowering medications, as well as no drug exposure, and cancer incidence. METHODS/DESIGN: This is a population based historical cohort study of all individuals aged 21 years or older (about 2,300,000) who were insured by Clalit Health Services, the largest health maintenance organization in Israel during a ten-year study period. Four study groups will be established according to the status of diabetes and cancer at study entry, Jan 1, 2002: cancer free, diabetes free; cancer free, diabetes prevalent; cancer prevalent, diabetes free; and cancer prevalent, diabetes prevalent. Individuals without diabetes at study entry will be followed for diabetes incidence, and all four groups will be followed for specific cancer incidence, including second primary neoplasms. Glucose control will be assessed by HbA1c and by fasting plasma glucose levels. Time dependent regression models for cancer incidence will account for glucose-lowering medications as they are added and changed over the follow-up period. A large number of demographic and clinical variables will be considered, including: age, gender, BMI, smoking status, concomitant medications, glucose control (assessed by HbA1c and by fasting plasma glucose) and cancer screening tests. DISCUSSION: Strengths of this study include the large population; high quality comprehensive data; comparison to individuals without diabetes, and to those with diabetes but not treated with glucose-lowering medications; and the extensive range of variables available for analysis. The great increases in diabetes prevalence and in treatment options render this study particularly relevant and timely. The Israeli national healthcare system, characterized by high standard and uniform healthcare, offers an advantageous environment for its conduct.

Intake of dietary phytoestrogens by Dutch women.

Higher consumption of phytoestrogens might be protective against certain chronic diseases. Accurate quantification of habitual phytoestrogen intake is important for assessing associations between phytoestrogens and risk for certain diseases. The aim of this study was to estimate dietary intake of phytoestrogens in Dutch middle-aged and elderly women and to describe their main sources. Women were recruited between 1993 and 1997 and aged 50-69 y at enrollment (Prospect-EPIC; n = 17,357). A detailed food frequency questionnaire referring to the preceding year was filled in at recruitment. A literature search was conducted to obtain data regarding content of the isoflavones daidzein, genistein, formononetin, biochanin A, the coumestan coumesterol and the lignans matairesinol and secoisolariciresinol in relevant food items. Concentrations of each phytoestrogen in each food item were subsequently grouped by seven categories; group scores were multiplied by daily intakes of food items and then summed across food items to produce for each participant a total daily intake score for each phytoestrogen. Approximately 75% of participants were postmenopausal at recruitment. The mean age was 57 y. Geometric means of daily intake of daidzein, genistein, formononetin, biochanin A, coumesterol, matairesinol and secoisolariciresinol were 0.15, 0.16, 0.08, 0.001, <0.001, 0.07 and 0.93 mg, respectively. The main sources for isoflavones were peas and beans, nuts, grain products, coffee, tea and soy products. The main sources for coumestans were peas, beans and other vegetables. The main sources of lignans were grain products, fruit and alcoholic beverages (red and white wines). We conclude that intake levels of phytoestrogen in our study population are low; however, they are comparable with intake levels previously reported for other Western cohorts. In this population, phytoestrogen intake consisted largely of lignans.

Cancer incidence in persons with Down syndrome in Israel.

The purpose of this study was to assess the incidence rates of leukaemia and other malignancies in persons with Down syndrome in Israel. The target population consisted of all persons with Down syndrome in the period of 1948-1995 and the study population was divided into two subgroups: (1) Persons born in Israel between 1979-95 (registry group) and (2) Persons currently or past-institutionalised, born before 1979 (institution group). The study population was linked to the Cancer Registry and cases that had been diagnosed through December 1995 were subsequently identified. The observed incidence rates were compared to expected rates in the general population. Standardised Incidence Ratios (SIR) and 95% confidence intervals were computed for each disease category. Analyses of results were performed separately for each subgroup of our study population. In the registry group seven cancer cases were observed as compared to 1.5 expected (SIR = 4.67 95% CI 1.9-9.6), all of which were leukaemia cases. For the institution group a total of 17 cancer cases were observed compared to 12.8 expected. These included four cases of leukaemia (SIR = 6.90 95% CI 1.9-17.7). An excess of gastric cancer in males, based on two cases (SIR = 11.9 95% CI 1.3-42.9) was also observed. The significant excess of leukaemia in the Down syndrome population in Israel is in accordance with other international studies. The excess of gastric cancer in males with Down syndrome, which has not been reported before, should be further explored.