Israel Medical Association Journal

Background: Israel has experienced three waves of coronavirus disease-2019 (COVID-19) infection since late February 2020, with lockdown and other measures employed to contain infection rates. In cooperation with the Israel Ministry of Health, serological testing was conducted by all four health maintenance organizations (HMO) in order to estimate national infection rates and the proportion of previously undetected disease.

Objectives: To estimate the proportion of the population that was seropositive, identify factors associated with seropositive outcome, and approximate the proportion of residents that were asymptomatic.

Methods: Seroconversion rates (IgG) were measured in a representative sample of over 17,000 members of Maccabi Healthcare Services. Direct standardization was used to estimate the seropositive rates for COVID-19 infection for members of the HMO. Rates were adjusted for sensitivity and specificity of the testing products used. In addition to blood sampling, respondents were asked to complete a digital survey regarding potential exposures and symptoms experienced.

Results: It was estimated that 1.9% of the adult HMO population was seropositive 4 months after the first infected person was identified in the country. Seroconversion was associated with travel abroad and exposure to infected individuals. Loss of smell and taste, fever, cough, and fatigue are associated with infection. Of those found to be seropositive for COVID-19, 160 (59%) had a prior negative polymerase chain reaction (PCR) or no PCR test at all.

Conclusions: Adult seropositive rates of infection were low relative to other countries. The findings suggest that early initiatives to limit infection entry and spread were effective

Background: High levels of plasma homocysteine constitute a risk for cardiovascular disease. Physical activity, known to reduce CVD[1] risk, has been related to levels of Hcy[2]. Recently, higher Hcy was shown to be associated with lower cardiovascular fitness in women but not in men.

Objectives: To further explore the relationship between cardiorespiratory fitness and plasma total homocysteine levels in a large cohort of adult males and females.

Methods: This cross-sectional study included 2576 fitness and Hcy examinations in adults (62% males) aged 30–59 years, randomly drawn from a population undergoing a periodic health examination in the Sheba Medical Center's Executive Screening Survey. Blood tests were collected for tHcy[3] and a sub-maximal exercise test was performed to estimate cardiorespiratory fitness. Information on CVD/CVD risk factors (coronary heart disease, cerebrovascular accident, diabetes, hypertension or dyslipidemia) was self-reported.

Results: Mean tHcy plasma levels were 14.4 ± 7.7 and 10.2 ± 3.0 µmol/ml, and mean maximal oxygen uptake 36.5 ± 11.7 and 29 2 ± 9.5 ml/kg/min for males and females, respectively. A multiple regression analysis, adjusting for age, body mass index and CVD/CVD risk factors, showed no association between cardiorespiratory fitness and level of tHcy in males (P = 0.09) or in females (P = 0.62).

Conclusions: In this sample no relationship was found between level of cardiorespiratory fitness and plasma tHcy in men or women. The inconsistency of findings and the small number of studies warrant further research of the association between cardiorespiratory fitness and tHcy, an association that may have clinical implications for the modifications of cardiovascular risk factors.

Background: Atherosclerosis is a chronic inflammatory process resulting in coronary artery disease.

Objectives: To determine the relationship between inflammatory markers and the angiographic severity of CAD[1].

Methods: We measured inflammatory markers in sequential patients undergoing coronary angiography. This included C-reactive protein, fibrinogen, serum cytokines (interleukin-1 beta, IL-1[2] receptor antagonist, IL-6, IL-8, IL-10) and tumor necrosis factor-alpha), all measured by high sensitivity enzyme-linked immunoabsorbent assay.

Results: There was a significant correlation between TNFα[3] and the severity of CAD as assessed by the number of obstructed coronary vessels and the Gensini severity score, which is based on the proximity and severity of the lesions. Patients had more coronary vessel disease (> 70% stenosis) with increasing tertiles of serum TNFα; the mean number of vessels affected was 1.15, 1.33, and 2.00 respectively (P < 0.001). IL-6 correlated with the Gensini severity score and coronary vessel disease (> 70% stenosis). A weaker correlation was present with IL-1 receptor antagonist. A significant correlation was not found with the other inflammatory markers. After adjustment for major risk factors, multivariate analyses showed that significant independent predictors of CAD vessel disease were TNFα (P < 0.05) and combined levels of TNFα and IL-6 (P < 0.05). IL-6 levels were independently predictive of Gensini coronary score (P < 0.05).

Conclusion: TNFa and IL-6 are significant predictors of the severity of coronary artery disease. This association is likely an indicator of the chronic inflammatory burden and an important marker of increased atherosclerosis risk.

Background: The precise genes involved in conferring prostate cancer risk in sporadic and familial cases are not fully known.

Objectives: To evlauate the genetic profile within several candidate genes of unselected prostate cancer cases and to correlate this profile with disease parameters.

Methods: Jewish Israeli prostate cancer patients (n=224) were genotyped for polymorphisms within candidate genes: p53, ER, VDR, GSTT1, CYP1A1, GSTP1, GSTM1, EPHX and HPC2/ELAC2, followed by analysis of the genotype with relevant clinical and pathologic parameters.

Results: The EPHX gene His113 allele was detected in 21.4% (33/154) of patients in whom disease was diagnosed above 61 years, compared with 5.7% (4/70) in earlier onset disease (P < 0.001). Within the group of late-onset disease, the same allele was noted in 5.5% (2/36) with grade I tumors compared with 18% (34/188) with grade II and up (P = 0.004). All other tested polymorphisms were not associated with a distinct clinical or pathologic feature in a statistically significant manner.

Conclusions: In Israeli prostate cancer patients, the EPHX His113 allele is seemingly associated with a more advanced, late-onset disease. These preliminary data need to be confirmed by a larger and more ethnically diverse study.

Background: Due to multiple chronic illness and disability, the elderly consume a disproportionately large share of medications.

Objectives: To assess the patterns and determinants of drug use among the community dwelling old-old population.

Methods: The study population included 1,369 old-old persons from the baseline data of the Cross-Sectional and Longitudinal Aging Study (CALAS), which is based on a national random stratified sample of the Israeli Jewish population aged 75–94 years.

Results: The mean number of drugs used by the study population was 3.3, and only 12.5% did not consume any drugs. Multivariate linear regression analysis showed that women used significantly more drugs than men, and that those born in Europe took significantly more drugs than those born in Israel and Asia-Africa. The number of medical conditions was the strongest predictor of drug use. Hospitalizations during the last year and frequent visits to family physician were also significant factors related to drug use. All variables combined explained 40% of the variance in drug use by the old-old. The most commonly used therapeutic groups were cardiovascular drugs (53%), psychotropic drugs (31%), analgesics (30%), and gastrointestinal drugs (28%).

Conclusions: Our data indicate that in addition to the association of drug use with health status and healthcare utilization, the number and type of drugs taken vary with gender and place of birth.