Israel Medical Association Journal

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: According to the U.S. Centers for Disease Control guidelines, prolonged rupture of membranes mandates intrapartum antimicrobial prophylaxis for group B Streptococcus whenever maternal GBS[1] status is unknown.

Objectives: To evaluate the local incidence, early detection and outcome of early-onset GBS sepsis in 35–42 week old neonates born after PROM[2] to women with unknown GBS status who were not given intrapartum antimicrobial prophylaxis.

Methods: During a 1 year period, we studied all neonates born beyond 35 weeks gestation with maternal PROM ≥ 18 hours, unknown maternal GBS status and without prior administration of IAP[3]. Complete blood count, C-reactive protein, blood culture and polymerase chain reaction amplification of bacterial 16S rRNA gene were performed in blood samples collected immediately after birth. Unfavorable outcome was defined by one or more of the following: GBS bacteremia, clinical signs of sepsis, or positive PCR[4].

Results:  Of the 3616 liveborns 212 (5.9%) met the inclusion criteria. Only 12 (5.7%) of these neonates presented signs suggestive of sepsis. PCR was negative in all cases. Fifty-eight neonates (27.4%) had CRP[5] > 1.0 mg/dl and/or complete blood count abnormalities, but these were not significantly associated with unfavorable outcome. Early-onset GBS sepsis occurred in one neonate in this high risk group (1/212 = 0.47%, 95% CI 0.012–2.6). 

Conclusions: In this single-institution study, the incidence of early-onset GBS sepsis in neonates born after PROM of ≥ 18 hours, unknown maternal GBS status and no intrapartum antimicrobial prophylaxis was 0.47%.

Background: Infections with blood-borne viruses are a major health problem among illicit drug users. There is little information about infection rates and risk factors for hepatitis virus B, C or the human immunodeficiency virus in drug users in Israel.

Objectives: To determine the prevalence of HCV[1], HBV[2] and HIV[3] infections in a large cohort of drug users in Israel; to compare rates of HCV, HBV and HIV between injecting versus non-injecting drug users and between different origin countries; and to identify risk factors for HCV among illicit drug users.

Methods: We conducted a cross-sectional interviewer-administered questionnaire and serological screening for HCV, HBV and HIV in 1443 consecutive drug users diagnosed at the Israeli National Center for Diagnosis of Drug Addicts between January 2003 and December 2005.

Results: Fourteen (0.9%), 51 (3.5%) and 515 (35.7%) subjects tested positive for HIV, HBV and HCV, respectively. All three infections (HIV, HBV and HCV) were significantly more common among injecting drug users and immigrants from the former Soviet Union and other East European countries compared to native Israelis. Multivariate analysis showed that HCV infection was associated with age (> 40 years) (OR=2.06, 95% CI 1.40–3.03), immigration from East European countries and the former Soviet Union (OR=4.54, 95% CI 3.28–6.28), and injecting drug use (OR=16.44, 95% CI 10.79–25.05).

Conclusions: HIV, HBV and HCV prevalence among drug users in Israel is significantly lower than in North America and West Europe. Risk factors for HCV infection in this population include injecting drug use, older age, and immigration from the former Soviet Union.

Background: General hospital staff are often required to care for physically ill patients who arouse concern regarding risk of harm to themselves or others. Some of these patients will receive one-to-one "constant observation." This is the first Israeli study of general hospital patients with high risk behavior.

Objectives: To examine a population of general hospital patients whose behavioral management required the use of constant observation. Demographic and clinical parameters including physical diagnoses were examined, and risk factors for constant observation were identified. The findings of this study were compared to findings in previous studies.

Methods: This prospective observational study examined 714 inpatients referred for psychiatric consultation; 150 were found to require constant observation, and 156 who did not served as a control group.

Results: In this study younger age, suicidal concerns and alcohol/substance abuse were identified as risk factors for ordering constant observation. Ischemic heart disease and chronic obstructive pulmonary disease were the only physical diagnoses found to be significantly correlated with a longer duration of observation, regardless of admission duration. Constant observation was less frequently used in the management of organic brain syndrome patients in this study compared to other studies.  

Conclusions: Some of our results (predictive factors for constant observation) confirmed the findings of overseas studies. Our finding that a diagnosis of organic brain syndrome was not a predictive factor for constant observation was unexpected and requires further investigation. The correlation between a diagnosis of ischemic heart disease or COPD[1] and duration of observation has not been reported previously and warrants further studies.  

Background: Erectile dysfunction is associated with treatable cardiovascular risk factors; therefore, screening for erectile dysfunction and its cardiovascular risk factors is of clinical importance.

Objectives: To detect erectile dysfunction cases and assess their severity among military personnel.

Methods: The Sexual Health Inventory for Men questionnaire was handed out to military personnel aged 25–55 years during routine examinations.

Results: A total of 19,131 men, with a mean age of 34.0 ± 7.1 years, participated in routine physical examinations during the years 2001–2005. More than half of them (n=9956, 52%) completed the SHIM[1] questionnaire. No significant differences were found between those who completed the SHIM questionnaire and those who did not, in terms of mean age, mean body mass index, and prevalence of cardiovascular risk factors. One out of every four men (25.2%) suffered from erectile dysfunction, which was mild in 18.9%, mild to moderate in 4.4%, moderate in 1.1% , and severe in 0.7%. Even though treatable cardiovascular risk factors were quite prevalent in the study group (45.2% of them suffered from dyslipidemia, 25.6% smoked, 4.2% suffered from essential hypertension, and 1.6% from diabetes mellitus), erectile dysfunction was significantly associated with age and diabetes mellitus alone (P < 0.0001).

Conclusions: There is a high prevalence of erectile dysfunction and associated treatable cardiovascular risk factors in Israeli men aged 25–55, especially those with diabetes. 

Background: Multi-detector computed tomography has advanced enormously and now enables non-invasive evaluation of coronary arteries as well as cardiac anatomy, function and perfusion. However, the role of cardiac MDCT[1] is not yet determined in the medical community and, consequently, many clinically unnecessary scans are performed solely on a self-referral basis.

Objectives: To prospectively evaluate the role of a cardiologist consultation and recommendation prior to the scan, and the influence on the diagnostic yield of cardiac MDCT.

Methods: In our center, a CT service was initiated, but with the prerequisite approval of a cardiologist before performance of the CT. Each individual who wanted and was willing to pay for a cardiac CT was interviewed by an experienced cardiologist who determined whether cardiac MDCT was the most appropriate next test in the cardiovascular evaluation. Subjects were classified into three groups: a) those with a normal or no prior stress test, no typical symptoms and no significant risk factors of coronary artery disease were recommended to perform a stress test or to remain under close clinical follow-up without MDCT; b) those with an equivocal stress test, atypical symptoms and/or significant risk factors were allowed to have cardiac MDCT; and c) those with positive stress test or clinically highly suspected CAD[2] were advised to go directly to invasive coronary angiography. CT findings were categorized as normal CAD (normal calcium score and no narrowings), < 50% and > 50% CAD.

Results: A total of 254 people were interviewed, and in only 39 cases did the cardiologist approve the CT. However, 61 of the 215, despite our recommendation not to undergo CT, decided to have the scan. Assessment of the 100 cases that underwent MDCT showed a statistically significant better discrimination of significant CAD, according to the cardiologist’s recommendation: MDCT not recommended in 3/54 (6%) vs. MDCT recommended in 12/39 (31%) vs. recommended invasive coronary angiography in 4/7 (57%) (P < 0.001).

Conclusions: Detection of coronary calcification, as well as MDCT angiography can provide clinically useful information if applied to suitable patient groups. It is foreseeable that MDCT angiography will become part of the routine workup in some subsets of patients with suspected CAD. Selection of patients undergoing MDCT scans by a cardiologist improves the ability of the test to stratify patients, preventing unnecessary scans in both high and low risk patients

Background: In view of the rising prevalence of obesity, the identification of young adult populations at risk is important for the formulation of intervention and prevention programs.

Objectives: To assess demographic and behavioral factors associated with an increase in body mass index in young healthy adults and to identify the incidence of overweight/obesity in this population.

Methods: Data on anthropometric measures, demographic characteristics, and health behaviors were collected retrospectively for a representative sample of young Israeli adults (11,391 men, 11,280 women) on their release from military service (age 20–22 years) between 1989 and 2003. The incidence of overweight (BMI[1] < 25-< 30 kg/m²), incidence of obesity (BMI ≥ 30 kg/m²), and increase in BMI during military service were calculated.

Results: The average increase in BMI during military service was 1.11 kg/m² in males and 1.08 kg/m² in females. A greater increase was positively associated with low paternal education and smoking cessation, and negatively associated with high physical activity. Twelve percent of subjects with a normal BMI on recruitment became overweight, and 21.7% of overweight subjects became obese. On multivariate logistic regression analysis, a higher incidence of overweight was associated with low education level (in both the subject and his or her father) in both genders, and non-use of oral contraceptives and low level of physical activity in females.

Conclusions: BMI appears to increase significantly during early adulthood. Intervention programs should be targeted specifically at subjects with low education or who started smoking before age 18, and physical activity (especially among females) should be encouraged.

Background: Intrapartum risk is based mainly on obstetric history, which is lacking in primiparous women.

Objectives: To ascertain whether the traditional known risk of primiparity is an independent variable for both maternal and neonatal outcome.

Methods: All women admitted to labor during March-April 2002 were canvassed for eligibility for participation in the study based on an obstetric risk scoring system developed and validated for our population. During the study period, 1473 women presented for delivery. Of these, 298 women (20%) were eligible according to the exclusion criteria as "low risk" parturients: 135 (45%) were primiparous and 163 (55%) were multiparous (2–5 births).

Results: After correction for significant confounding factors, primiparity was revealed as an independent significant risk factor for instrumental delivery (odds ratio 15.5, 95%confidence interval 1.88–125) and for early postpartum hemorrhage (OR[1] 5.6, 95%CI[2] 1.9–16.6).

Conclusions: This study highlights early postpartum hemorrhage as a significant risk for primiparous women, independent of mode of delivery, and also confirms previous reports of maternal complications requiring transfer from birth centers/home deliveries to tertiary centers.

Background: Idiopathic frozen shoulder is a self-limiting regional skeletal problem of unknown etiology. Clinically, patients first experience a phase of pain, progressing to a freezing stage when glenohumeral motion is lost, followed by a thawing phase when pain gradually subsides and most of the lost motion returns.

Objectives: To identify possible specific and non-specific risk factors for idiopathic frozen shoulder.

Methods: We compared the medical histories, drug treatment, previous hospital as well as health management organization blood tests of 126 new consecutive frozen shoulder patients from a shoulder clinic to those of an age-matched control group of 98 consecutive patients from an orthopedic foot and ankle clinic and to the regional population disease prevalence registry. Frozen shoulder was classified as idiopathic only if there was no history of trauma and no evidence of a rotator cuff tear.

Results: Among the frozen shoulder patients 29.4% had diabetes and 13.5% had thyroid disorders. The risk ratio for diabetes in the frozen shoulder group was 5.9 for males (95% confidence interval 4.1–8.4, P < 0.001) and 5.0 for females (95% CI[1] 3.3–7.5, P < 0.001). The risk ratio for thyroid disorders among females with frozen shoulder was 7.3 (95% CI 4.8–11.1, P = 0.001). No significant difference was found in the prevalence of thyroid disorders between frozen shoulder and the control group, but there was a significantly higher prevalence of diabetes in males and a trend for higher prevalence in females in the frozen shoulder group.

Conclusions: Physicians should be aware that diabetes is a specific risk factor for idiopathic frozen shoulder in both males and females and thyroid disorders are a non-specific risk factor in females only.  

Background: Carotid artery stenting is used as an alternative to surgical endarterectomy.

Objectives: To determine the outcome of CAS[1] in a retrospective cohort of patients.

Methods: Between July 1999 and March 2003, 56 consecutive patients with carotid artery stenosis who were considered ineligible for surgery were treated (45 male, 11 female, mean age 69). All cases were performed prior to the introduction of distal protective devices in Israel.

Results: Intraprocedural complications included transient neurological findings in 5 patients (8%), cerebrovascular accident in 2 (3%), hemodynamic changes in 11 (18%), and 4 procedural failures. Post-procedural complications included transient ischemic attack in 3 patients and cardiovascular accident in 6 (10%). At 30 days follow-up, three patients (5%) remained with signs of CVA[2]. Two patients (3%) died during the post-procedural period and 16 (28%) during the 5 year follow-up, one due to recurrent CVA and the remainder to non-neurological causes. Five-year carotid Doppler follow-up was performed in 25 patients (45%), which revealed normal stent flow in 21 (84%), 50–60% restenosis in 3 patients (12%) and > 70% restenosis in one patient (4%).

Conclusions: This study confirms that stent procedures are beneficial for symptomatic carotid stenosis in patients not eligible for surgery.

Background: Falls are a common problem among hospitalized patients, having a significant impact on quality of life and resource utilization.

Objectives: To develop and validate a fall-risk assessment tool for patients hospitalized in the department of medicine that will combine simplicity with adequate accuracy for routine use.

Methods: This observational cohort study was conducted on the medical wards of an urban tertiary teaching hospital, and included all patients who fell in the medical wards during a 1 year period (n=140) compared to other hospitalized patients.

Results: Significant correlates of falls were previous falls, impairing medical conditions, impaired mobility, and altered mental state. In multivariate logistic regression analyses, only previous falls (odds ratio 3.8 with 95% confidence interval 2.65–5.45, P < 0.0001) and acute impairing medical conditions (OR[1] 1.56, CI[2] 1.06–2.29, P < 0.05) correlated independently with a higher risk for falls. Impaired mobility retained an OR of 1.46 (CI 0.95–2.24, P = 0.084). Accordingly, defining patients with either a history of previous falls or both acute impairing medical state and impaired mobility as fall-prone patients provided a sensitivity and specificity of 67% and 63%, respectively. In a subsequent prospective validation trial on 88 patients who fell during hospitalization and 436 controls, the sensitivity and specificity of this fall-risk grouping were 64% and 68% respectively.

Conclusions: Our new simple and easy-to-use fall-risk assessment tool identified most of the fall-prone patients. These findings suggest that using this tool may enable us to prevent two-thirds of falls on the medical ward by providing effective fall-prevention facilities to only one-third of the patients.

Background: Germline mutations in BRCA1 and BRCA2 genes account for only 20–40% of familial breast cancer cases. The CHEK2 gene encodes a checkpoint kinase, involved in response to DNA damage, and hence is a candidate gene for breast cancer susceptibility. Indeed, the CHEK2*1100delC truncating mutation was reported in a subset of mostly North European breast cancer families. The rate of the CHEK2*1100delC variant in the Ashkenazi* Jewish population was reported to be 0.3%.

Objectives: To evaluate whether CHEK2 germline mutations contribute to a breast cancer predisposition in Ashkenazi-Jewish high risk families.

Methods: High risk Ashkenazi Jewish women, none of whom was a carrier of the predominant Jewish mutations in BRCA1/BRCA2, were genotyped for germline mutations in the CHEK2 gene by exon-specific polymerase chain reaction followed by denaturing gradient gel electrophoresis and sequencing of abnormally migrating fragments.

Results: Overall, 172 high risk women were genotyped: 75 (43.6%) with breast cancer (average age at diagnosis 49.6 ± 9.6 years, mean ± SD) and 97 asymptomatic individuals (age at counseling 48.3 ± 8.2 years). No truncating mutations were noted and four previously described missense mutations were detected (R3W 1.2%, I157T 1.2%, R180C 0.6% and S428F 5%), one silent polymorphism (E84E 20.5%) and one novel missense mutation (Y424H 1.2%). Segregation analysis of the I157T and S428F mutations (shown to affect protein function) with the cancer phenotype showed concordance for the CHK2*I157T mutation, as did two of three families with the CHK2*S428F mutation.

Conclusions: CHEK2 missense mutations may contribute to breast cancer susceptibility in Ashkenazi Jews.

Background: Until three decades ago coronary heart disease and stroke were considered rare in the Israeli Bedouin population. Today, this population shows increasing high prevalence compared to the Jewish population.

Objectives: To evaluate the prevalence of diagnosed cardiovascular risk factors among the Bedouin (hypertension, diabetes mellitus, dyslipidemia), and to assess compliance with follow-up tests and drug treatment.

Methods: The study included all listed patients aged 20 years and older in eight clinics in major Bedouin towns, and in two large teaching clinics in Beer Sheva (Jewish population). Risk factor data were extracted from the clinics' computerized databases. For those diagnosed with hypertension, diabetes or dyslipidemia, drug purchasing data were collected from the pharmacy database to determine compliance with treatment, and from the central laboratory mainframe (HbA1c and low density lipoprotein-cholesterol) to evaluate follow-up and control.

Results: A significantly higher prevalence of diabetes in all age groups was found in the Bedouin population compared to the Jewish population; age-adjusted results show a prevalence of 12% vs. 8% respectively (P < 0.001). The prevalence of dyslipidemia and age-adjusted hypertension was lower among Bedouins (5.8% vs. 18.2%, P < 0.01 and 17% vs. 21%, P < 0.001 respectively). Two-thirds of hypertensive Bedouin patients and 72.9% of diabetic Bedouin patients were not compliant with treatment. For dyslipidemia only 10.4% of the Bedouins were compliant compared with 28.2% in the Jewish population (P < 0.001).

Conclusions: Compliance with drug therapy and follow-up tests was found to be a major problem in the Bedouin population.
 

Background: Age-related macular degeneration is the most common cause of legal blindness in the developed world including Israel. Ethnic background is a risk factor for advanced AMD[1] in several populations, however the relative prevalence of this disease in different ethnic groups in the Middle East is unknown.

Objectives: To compare the prevalence of advanced AMD in Arabs and Jews in Israel.

Methods: We performed a retrospective analysis of two independent groups of patients: the first group comprised a sequential series of Jerusalem residents who underwent photodynamic therapy for neovascular AMD (PDT[2] group), and the second group consisted of all individuals in Jerusalem who received a blind certificate due to AMD (legal blindness group). Control groups were assessed to exclude inherited ethnic associated bias in the two study groups.

Results: The PDT group included 146 patients: 142 were Jews (97.3%) and 4 were Arabs (2.7%). The legal blindness group included 340 Jerusalem residents: 326 Jews (96%) and 14 Arabs (4%). The number of Arab AMD patients in the two groups was lower than expected based on the ethnic composition of the age-matched Jerusalem population (P = 0.0002 for the PDT group, and P < 0.0001 for the legal blindness group). By contrast, the number of non-AMD Arab patients who were treated in the same clinic and the number of Arabs who received a blind certificate for diabetic retinopathy was not different from expected based on their relative number in the Jerusalem population.

Conclusions: Advanced AMD is less common in the Arab than the Jewish population of Jerusalem. Genetic and environmental factors may account for this difference. A population-based study is required to assess the overall prevalence of AMD in Jews and Arabs.