Myocarditis after BNT162b2 mRNA Vaccine against Covid-19 in Israel.

BACKGROUND: Approximately 5.1 million Israelis had been fully immunized against coronavirus disease 2019 (Covid-19) after receiving two doses of the BNT162b2 messenger RNA vaccine (Pfizer-BioNTech) by May 31, 2021. After early reports of myocarditis during adverse events monitoring, the Israeli Ministry of Health initiated active surveillance. METHODS: We retrospectively reviewed data obtained from December 20, 2020, to May 31, 2021, regarding all cases of myocarditis and categorized the information using the Brighton Collaboration definition. We analyzed the occurrence of myocarditis by computing the risk difference for the comparison of the incidence after the first and second vaccine doses (21 days apart); by calculating the standardized incidence ratio of the observed-to-expected incidence within 21 days after the first dose and 30 days after the second dose, independent of certainty of diagnosis; and by calculating the rate ratio 30 days after the second dose as compared with unvaccinated persons. RESULTS: Among 304 persons with symptoms of myocarditis, 21 had received an alternative diagnosis. Of the remaining 283 cases, 142 occurred after receipt of the BNT162b2 vaccine; of these cases, 136 diagnoses were definitive or probable. The clinical presentation was judged to be mild in 129 recipients (95%); one fulminant case was fatal. The overall risk difference between the first and second doses was 1.76 per 100,000 persons (95% confidence interval [CI], 1.33 to 2.19), with the largest difference among male recipients between the ages of 16 and 19 years (difference, 13.73 per 100,000 persons; 95% CI, 8.11 to 19.46). As compared with the expected incidence based on historical data, the standardized incidence ratio was 5.34 (95% CI, 4.48 to 6.40) and was highest after the second dose in male recipients between the ages of 16 and 19 years (13.60; 95% CI, 9.30 to 19.20). The rate ratio 30 days after the second vaccine dose in fully vaccinated recipients, as compared with unvaccinated persons, was 2.35 (95% CI, 1.10 to 5.02); the rate ratio was again highest in male recipients between the ages of 16 and 19 years (8.96; 95% CI, 4.50 to 17.83), with a ratio of 1 in 6637. CONCLUSIONS: The incidence of myocarditis, although low, increased after the receipt of the BNT162b2 vaccine, particularly after the second dose among young male recipients. The clinical presentation of myocarditis after vaccination was usually mild.

SARS-CoV-2 and seasonal influenza: similarities and disparities.

This report describes the differences in disease severity and clinical presentation between hospitalized patients with coronavirus disease 2019 (COVID-19) and others with seasonal influenza. A total of 136 influenza and 152 COVID-19 patients were included. Patients with influenza more frequently had dyspnea (p = 0.004), hypoxemia (p < 0.001), underlying diseases (p = 0.046), and elevated liver enzymes (p = 0.028). In contrast, patients with COVID-19 were overweight (p < 0.001), lymphopenic (p < 0.001), had elevated CRP (p = 0.011), and radiological abnormalities (p < 0.001). Patients with influenza were more severely ill on admission (NEWS > 5) (p < 0.001). However, length of hospital stay, ventilatory support, and 30-day-mortality were similar. Despite differences in clinical presentation and disease severity between influenza and COVID-19 patients, both groups had similar clinical outcomes.

Gender differences in measles incidence rates in a multi-year, pooled analysis, based on national data from seven high income countries.

BACKGROUND: Gender differences in a number of infectious diseases have been reported. The evidence for gender differences in clinical measles incidence rates has been variable and poorly documented over age groups, countries and time periods. METHODS: We obtained data on cases of measles by sex and age group over a period of 11-27 years from seven countries. Male to female incidence rate ratios (IRR) were computed for each year, by country and age group. For each age group, we used meta-analytic methods to combine the IRRs. Meta-regression was conducted to the estimate the effects of age, country, and time period on the IRR. RESULTS: In the age groups < 1, 1-4, 5-9, 10-14, 15-44, and 45-64 the pooled IRRs (with 95% CI) were 1.07 (1.02-1.11), 1.10 (1.07-1.14), 1.03 (1.00-1.05), 1.05 (0.99-1.11), 1.08 (0.95-1.23), and 0.82 (0.74-0.92) respectively. The excess incidence rates (IR) from measles in males up to age 45 are remarkably consistent across countries and time-periods. In the age group 45-64, there is an excess incidence in women. CONCLUSIONS: The consistency of the excess incidence rates in young males suggest that the sex differences are more likely due to physiological and biological differences and not behavioral factors. At older ages, differential exposure can play a part. These findings can provide further keys to the understanding of mechanisms of infection and tailoring vaccination schedules.

A meta-analytic evaluation of sex differences in meningococcal disease incidence rates in 10 countries.

The magnitude and consistency of the sex differences in meningococcal disease incidence rates (IR) have not been systematically examined in different age groups, countries and time periods. We obtained national data on meningococcal disease IR by sex, age group and time period, from 10 countries. We used meta-analytic methods to combine the male to female incidence rate ratios (IRRs) by country and year for each age group. Meta-regression analysis was used to assess the contribution of age, country and time period to the variation in the IRRs. The pooled male to female IRRs (with 95% CI) for ages 0-1, 1-4, 5-9, 10-14 and 15-44, were 1.25 (1.19-1.32), 1.24 (1.20-1.29), 1.13 (1.07-1.20), 1.21 (1.13-1.29) and 1.15 (1.10-1.21), respectively. In the age groups 45-64 and over 65, the IR were lower in males with IRRs of 0.83 (0.78-0.88) and 0.64 (0.60-0.69), respectively. Sensitivity analysis and meta-regression confirmed that the results were robust. The excess meningococcal IR in young males and the higher rates in females at older ages were consistent in all countries, except the Czech Republic. While behavioural factors could explain some of the sex differences in the older age groups, the excess rates in very young males suggest that genetic and hormonal differences could be important.

Sex differences in campylobacteriosis incidence rates at different ages - a seven country, multi-year, meta-analysis. A potential mechanism for the infection.

BACKGROUND: There is evidence that males have higher incidence rates (IR) of campylobacteriois than females. The objectives of this study were to determine whether these observations differ between age groups and are consistent over different countries and during different time periods. METHODS: We obtained data on IRs of campylobacteriosis by sex and age group over a period of 11-26 years from seven countries. Male to female incidence rate ratios (IRR) were computed by age group, country and time period. For each age group, we used meta-analytic methods to combine the IRRs. Sensitivity analysis was used to test whether the results are robust to differences between countries and time periods. Meta-regression was conducted to estimate the different effects of age, country, and time period on the IRR. RESULTS: In the age groups < 1, 1-4, 5-9, 10-14, 15-44, 45-64 and 65+ years old, the pooled IRRs (with 95% CI) were 1.31 (1.26-1.37), 1.34 (1.31-1.37), 1.35 (1.32-1.38), 1.73 (1.68-1.79), 1.10 (1.08-1.12), 1.19(1.17-1.21) and 1.27 (1.24-1.30), respectively. For each age group, the excess campylobacteriosis IRs in males differed at different age groups. However, despite some quantitative differences between countries, the excess was consistently present over long time-periods. In meta-regression analysis, age group was responsible for almost all the variation in the IRRs. CONCLUSIONS: The male predominance in campylobacteriosis IRs starts in infancy. This suggests that this is due, at least in part, to physiological or genetic differences and not just behavioural factors. These findings can provide clues to the mechanisms of the infection and could lead to more targeted treatments and vaccine development.

Sex differences in shigellosis incidence rates: analysis of national data from nine countries using meta-analytic method.

BACKGROUND: Sex differences in the incidence of infectious diseases can provide insight to the biological mechanism of infection, disease susceptibility, severity and vaccine development. The consistency of age-specific sex differences in the incidence rates (IRs) of shigellosis is unclear. METHODS: National data on cases of shigellosis by sex, age group and calendar year were obtained from nine countries, for a period of 6-25 years. The male to female incidence rate ratios (RR) were calculated by country, years and age group. For each age group, meta-analytic methods were used for computing pooled incidence RRs by country and years. Meta-regression was performed to estimate the contribution of age, country and time period to the differences in the male : female RRs. RESULTS: In the age groups <1, 1-4, 5-9 and 10-14, there were excess IRs in males. The pooled incidence RRs (with 95% CI) were 1.21 (1.14-1.28), 1.17 (1.12-1.22), 1.04 (1.00-1.09) and 1.09 (1.01-1.18), respectively. In young adults, there was excess IR in females with RR = 0.80 (0.72-0.9). In middle aged and older adults, there was a slight excess in males with RR = 1.01 (0.89-1.15) and RR = 1.18 (1.09-1.28), respectively. In the meta-regression, age was the only variable that significantly contributed to the variation in the RRs. CONCLUSIONS: The higher IRs in male infants and young children does not appear to be related to behavioral factors and genetic and hormonal factors could be important. In the older age groups, the higher rates in adult females may be due to behavioral factors.

Inequalities in non-communicable diseases between the major population groups in Israel: achievements and challenges.

Israel is a high-income country with an advanced health system and universal health-care insurance. Overall, the health status has improved steadily over recent decades. We examined differences in morbidity, mortality, and risk factors for selected non-communicable diseases (NCDs) between subpopulation groups. Between 1975 and 2014, life expectancy in Israel steadily increased and is currently above the average life expectancy for the Organisation for Economic Co-operation and Development countries. Nevertheless, life expectancy has remained lower among Israeli Arabs than Israeli Jews, and this gap has recently widened. Age-adjusted mortality as a result of heart disease, stroke, or diabetes remains higher in Arabs, whereas age-adjusted incidence and mortality of cancer were higher among Jews. The prevalence of obesity and low physical activity in Israel is considerably higher among Arabs than Jews. Smoking prevalence is highest for Arab men and lowest for Arab women. Health inequalities are also evident by the indicators of socioeconomic position and in subpopulations, such as immigrants from the former Soviet Union, ultra-Orthodox Jews, and Bedouin Arabs. Despite universal health coverage and substantial improvements in the overall health of the Israeli population, substantial inequalities in NCDs persist. These differences might be explained, at least in part, by gaps in social determinants of health. The Ministry of Health has developed comprehensive programmes to reduce these inequalities between the major population groups. Sustained coordinated multisectoral efforts are needed to achieve a greater impact and to address other social inequalities.

Estimation and development of 10- and 20-year cardiovascular mortality risk models in an industrial male workers database.

We examined the performance of the Framingham Heart Study (FHS) and the European Systematic Coronary Risk Evaluation (SCORE) models for cardiovascular disease (CVD) mortality prediction in Israeli industrial workers, and developed and validated new risk prediction models for CVD mortality incidence in the same population. Our database was a longitudinal Israeli industrial cohort (CORDIS cohort) of 4809 adult males followed-up for 22years. Performance of the FHS and the SCORE prediction models was analyzed by insertion of the CORDIS cohort measurements to each model separately. The standard prognostic variables and results obtained from the new refined Cox regression analyses were used to construct two new 10- and 20-year CVD mortality risk scoring systems: a modified FHS model (FHS/Cox) and an omnibus model with Cox regression (Omnibus/Cox). The SCORE model of high-risk and low-risk charts yielded 10-year mortality mean risks of 1.12% and 0.64%, respectively, for male subjects aged>30years. The new FHS/Cox and Omnibus/Cox models generated a mean predictive 10-year risk of 1.12% and 1.50%, respectively. The mean 20-year risk predicted by the new FHS/Cox and the Omnibus/Cox models was 2.66% and 3.75%, respectively. Internal validation of both models demonstrated a high and stable area under the receiver operating characteristic curve>0.85. No significant differences were found between the two models. In conclusion, the CVD mortality risk prediction scoring systems tailored for the Israeli workers population demonstrated good performance. Additional studies to externally validate these algorithms will indicate which of these quantitative risk estimation platforms should be used in specific settings.

Association between second-hand smoking and acute coronary heart disease among Arab women with multiple risk factors.

BACKGROUND: Active smoking is a well-established risk factor for coronary heart disease (CHD). However, the role of second-hand smoking (SHS) needs further investigation. We aimed to study the association between SHS and CHD in Arab women in Israel. METHODS: A matched case-control study among non-smoking Arab women. The case group included women discharged from hospital after having acute coronary event. The control group was women without CHD who were individually matched for age and type-2 diabetes. The women were interviewed with structured questionnaires on exposure to SHS and on attitudes towards such exposure, and underwent anthropometric measurements. RESULTS: A total of 146 women were included, the majority had type-2 diabetes (68.5%) and were overweight or obese (89.4% of cases and 93.2% of controls, P = 0.727). The prevalence of exposure to domestic-SHS after marriage was higher among the cases than controls (91.8% vs. 53.4%, P < 0.001). After adjustment for hypertension, body mass index > 25 and family history, exposure to domestic-SHS after marriage was an independent risk factor for CHD (OR = 6.1, 95% CI 1.93-19.3). Compared with no exposure, the exposed for 2-6 h a day had an OR of 5.68 (1.48-21.73), and for >6 h a day the OR reached 26.12 (4.26-159.92). Women with CHD felt less comfortable voicing their concern about smoking near them and more highly agreed with prohibition of smoking. CONCLUSIONS: Exposure to domestic-SHS is independently associated with CHD in Arab women, with a strong dose-response relationship, emphasizing the need for public health initiatives to reduce exposure to domestic-SHS.

The prevalence of gestational diabetes mellitus recurrence--effect of ethnicity and parity: a metaanalysis.

Reports on the gestational diabetes mellitus (GDM) recurrence rate have been highly variable. Our objectives were to examine the possible causes of GDM recurrence rate variability and to obtain pooled estimates in subgroups. We have carried out a systematic review and metaanalysis based on the Metaanalysis Of Observational Studies in Epidemiology statement. We identified papers published from 1973 to September 2014. We identified papers using Medline (PubMed and Ovid), ClinicalTrials.gov and Google Scholar databases, and published references. We included only English-language, population-based studies that reported specified GDM criteria and GDM recurrence rate. A total of 18 eligible studies with 19,053 participants were identified. We used the Cochrane's Q test of heterogeneity to choose the model for estimating the pooled GDM recurrence rate. Metaregression was also used to explore the possible causes of variability between studies. The pooled GDM recurrence rate was 48% (95% confidence interval, 41-54%). A significant association between ethnicity and GDM recurrence rate was found (P = .02). Non-Hispanic whites had lower recurrence rate compared with other ethnicities (39% and 56%, respectively). Primiparous women had a lower recurrence rate compared with multiparous women (40% and 73%, respectively; P < .0001) No evidence for association between family history of diabetes and GDM recurrence was found. The overall GDM recurrence rate is high. Non-Hispanic whites and primiparous women have substantially lower GDM recurrence rates, which contributes to the variability between studies. Because no association between family history of diabetes and GDM recurrence was found, the large differences between ethnic groups may have also resulted from nongenetic factors. Thus, intervention programs could reduce the GDM recurrence rates.

Combined association of occupational and leisure-time physical activity with all-cause and coronary heart disease mortality among a cohort of men followed-up for 22 years.

OBJECTIVES: Leisure-time physical activity (LTPA) is a well-established protective factor for all-cause mortality and cardiovascular mortality while occupational physical activity (OPA) has shown contradictory results. We examined the association between OPA and all-cause and coronary heart disease (CHD) mortality, and tested its combined effect with LTPA. METHODS: The CORDIS Study (Cardiovascular Occupational Risk Factor Determination in Israel Study) is a prospective cohort study of industrial workers examined during 1985-1989 and followed-up for 22 years. Data on self-reported OPA and LTPA among 4819 males (20-70 years old) were merged with data on all-cause and CHD mortality obtained from the National Death Registry. RESULTS: A higher incidence rate of all-cause mortality and CHD mortality was observed among men who performed moderate-hard OPA compared with those who performed none-mild OPA. Multiple regression analysis based on the Cox proportional hazards model showed that moderate-hard OPA was associated with increased risk of all-cause mortality (HR=1.42, 95% CI 1.16 to 1.74, p<0.001), while LTPA (30 min at least twice a week vs less or none) was associated with reduced risk for all-cause mortality (HR=0.61, 95% CI 0.48 to 0.79, p<0.001), after adjusting for potential confounders, including sociodemographic variables, body mass index, comorbidity and lifestyle habits. Employees who performed moderate-hard OPA and no LTPA had the greatest risk for all-cause mortality and employees who performed none-light OPA and LTPA had the lowest risk. Similar but non-significant trends were observed for the association with CHD mortality. CONCLUSIONS: Moderate-hard OPA among industrial male workers may be deleterious to health and should not be a substitute to LTPA.

Effect of adherence to evidence-based therapy after acute myocardial infarction on all-cause mortality.

PURPOSE: Our aim is to estimate the effect of nonadherence to evidence-based cardioprotective medications on all-cause mortality in survivors of acute myocardial infarction (AMI). METHODS: A patient-based retrospective cohort study of 1-year survivors of AMI, members of a health organization in Israel, between 2005 and 2010 was used. Adherence was measured using the proportion-of-days-covered metric and defined as a proportion of days covered ≥80%. In order to determine the independent impact of medication nonadherence on all-cause mortality, Cox proportional hazards models were constructed, adjusting for patient demographic and clinical characteristics. RESULTS: Of 4655 patients prescribed at least one medication, 864 died during an 8-year follow-up (median 4.5 years). Except for beta-blockers, medication nonadherence was significantly associated with increased adjusted all-cause mortality risk for aspirin [hazard ratio (HR), 1.28; 95% confidence interval (CI), 1.11-1.47], statins (HR, 1.36; 95%CI, 1.18-1.57), and angiotensin-converting enzyme inhibitors/angiotensin receptor blockers only among ischemic heart disease patients with documented heart failure (HR, 1.57; 95%CI, 1.16-2.14). Multidrug-combined therapy exerted incremental survival benefit in a dose-response gradient, exceeding that of single-component treatment. The highest risk of mortality was observed in patients adherent to none of the medications compared with adherents to all medications, with a 38% increase in risk of mortality (HR, 1.38; 95%CI, 1.06-1.80). CONCLUSIONS: Outpatient nonadherence to evidence-based cardioprotective medications in patients with AMI is common, and in the case of aspirin, statin or combined therapy is associated with a marked risk increase in all-cause mortality. Further research is needed to elucidate the role of angiotensin-converting enzyme inhibitor/angiotensin receptor blocker in patient subgroups.

Voluntary or Mandatory? The Valence Framing Effect of Attitudes Regarding HPV Vaccination.

This study addresses the issue of valence framing effect in the context of immunization, a preventive behavior often addressed by the equation of benefit versus risk. The authors examined how framing (support vs. oppose) the issue of HPV vaccination in Israel's immunization routine affects attitudes regarding vaccine regulations. The study also examined issue involvement as a moderator of valence framing effect. The results demonstrate that participants in the positive framing condition tended to express greater support for voluntary immunization than participants in the negative framing condition (77.5% and 48.5%, respectively). Among those who supported the mandatory HPV immunization policy, the negative framing condition was more prominent than the positive condition (51.5% and 22.5%, respectively). The analysis of interaction between valence framing and issue involvement showed that the latter tends to moderate the direct effect of framing on attitudes towards vaccination. Findings indicate that even attitudes towards such consequential preventive behaviors as vaccination could be affected by different framing of the issue, especially for those who are less involved. Implications of predilection for freedom of choice regarding vaccination are also discussed.

Significant cross reactive antibodies to influenza virus in adults and children during a period of marked antigenic drift.

BACKGROUND: Little is known about the development of cross-reactive antibodies following natural exposure to pathogens. Such knowledge is critical in the development of new universal influenza vaccines. METHODS: To study the possibility of the presence of cross-reactive antibodies to influenza viruses which underwent a major antigenic drift between the years 1999 and 2007 sera from samples of 80 children and 400 adults were selected at random from the Israeli national serum bank. The sera was obtained in 2002 and in 2007, two time points that followed a major drift in the infectious H3N2 influenza virus strain (A/Panama/2007/99 to A/Wisconsin/67/2005). RESULTS: In the summer of 2002, 13% of the children had Hemagglutination Inhibition (HI) antibody titers of at least 40 and these antibodies recognized both A/Panama/2007/99 and A/Wisconsin/67/2005, where the latter strain only began to circulate in Israel in 2006. In 2007, 29% of the children had HI antibody titers of at least 40 directed against both A/Wisconsin/67/2005 and A/Panama/2007/99, even though they had never been exposed to the latter virus. Anti-A/Panama/2007/99 antibodies were detected in 58% and 68% of the 2002 and 2007 adult samples, respectively, while 8% and 39% had antibodies against A/Wisconsin/67/2005, respectively. CONCLUSIONS: The presence of naturally occurring cross-reactive influenza virus antibodies in a significant percentage of children has important implications for the development of a universal influenza vaccine.

Assessing the Impact of a Designated Pharmacist Intervention on Drug Treatment Costs and Technical Efficiency in the Hemato-Oncology Outpatient Clinic.

OBJECTIVES: This study aimed to investigate the impact of a designated pharmacist (DPha) intervention in a hemato-oncology unit, focusing on reducing drug treatment costs and improving technical efficiency (TE). METHODS: Data from an 8-month intervention in the Israeli Clalit Health Services hemato-oncology outpatient unit were analyzed. During the study, the DPha reviewed the drug therapies being administered. After the review, a recommendation letter was sent, if relevant, to the treating physician. Data on drug treatment costs and interventions were meticulously collected and analyzed from the perspective of the insurer. A simple design was used to assess the DPha intervention's contribution to TE and cost reduction, which was used to generate credible and transparent estimates. Sensitivity analyses were conducted to assess the robustness of 2 major variables: drug prices and pharmacist salaries. RESULTS: Over 8 months, DPha interventions led to a $279 191 cost reduction for 91 patients, resulting in net savings of $269 420 ($2960 per patient). Noteworthy is the $411 savings for each hour worked by the pharmacist, with a major impact on medications not insurer approved for the patient's condition ($101 151) and discontinuing inappropriate medications ($52 681). Biological drug optimization accounted for 81% of total savings. Sensitivity analyses demonstrated significant cost savings across various drug prices and pharmacist salary scenarios. CONCLUSIONS: The study proposes a practical framework for optimizing pharmacist services and reducing the inappropriate use of costly oncology medications. Incorporating a DPha enhances TE and yields significant cost reductions, offering valuable insights for insurers, policy makers, and healthcare professionals.