Israel Medical Association Journal

Objectives: To examine whether the treatment recommendations given to ischemic heart disease patients at hospital discharge are compatible with the guidelines of the Israeli Medical Societies and the U.S. National Cholesterol Education Program for coronary artery disease prevention; and to study the effects of brief educational sessions on the adherence of physicians with the guidelines.

Methods: We included consecutive IHD[1] patients admitted to four central hospitals in Israel between 1998 and 2000. The study was conducted in two phases. In phase 1, we reviewed discharge letters to document treatment recommendations given to each patient. In phase 2 we educated the practitioners by reviewing the Israeli Medical Societies and the NCEP[2] guidelines and the quality of their recommendations in phase 1, after which we reevaluated the discharge letters.

Results: The study included 2,994 patients: 627 in phase 1 and 2,367 in phase 2. Of the patients who needed cholesterol-lowering according to their low density lipoprotein levels, 37.4% were not prescribed such drugs at discharge (under-treatment group). This proportion was reduced by education to 26.6% (P < 0.001) in phase 2. Of the treated patients, 65.6% did not reach the target LDL[3] goal in phase 1 (under-dosage group) as compared to 60.2% in phase 2 (P = 0.23). In phase 2 there was an increase in the percent of patients reaching LDL levels <130 mg/day (69.3% vs. 63.8% of patients prescribed medication, P = 0.01), but the percent of patients reaching LDL levels <100 was not different in phase 2 after adjusting for age and gender (the odds ratio for reaching target LDL was 1.16, with 95% confidence interval of 0.95–1.43).

Conclusions: Physician recommendations to IHD patients discharged from hospital were suboptimal. We documented a high proportion of under-treated and under-dosage patients. Brief educational sessions have a beneficial effect on the usage of statins; however, additional effort in guideline implementations is needed.

Objectives: To describe and analyze how PCPs[1] in the IDF[2] view their roles as primary care providers and to characterize how they perceive the quality of the medical care that they provide.

Methods: We conducted a survey using a questionnaire that was mailed or faxed to a representative sample of PCPs. The questionnaire included demographic background, professional background, statements on self-perception issues, and ranking of roles as a PCP in the IDF.

Results: Statements concerning commitment to the patient were ranked higher than statements concerning commitment to the military organization. Most physicians perceive the quality of the medical care service that they provide as high; they also stated that they do not receive adequate continuous medical education.

Conclusions: Our survey shows that PCPs in the IDF, like civilian family physicians, perceive their primary obligation as serving the needs of their patients but are yet to take on the full role of “gatekeepers” in the IDF’s healthcare system. We conclude that the Medical Corps should implement appropriate steps to ensure that PCPs are prepared to take on a more prominent role as “gatekeepers” and providers of high quality primary medical care.

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[1] PCP = primary care physician

[2] IDF = Israel Defense Force

Background: Oral contraceptive users are at increased risk for both arterial and venous thrombosis, some of which can be fatal. Studies are consistent with the existence of a synergism between cigarette smoking and OC[1] use in the pathogenesis of myocardial infarction in young women.

Objectives: To study the relationship between OC use, cigarette smoking and other cardiovascular risk factors among young women.

Methods: A systematic sample of military personnel, upon discharge from service in the Israel Defense Forces, was asked to complete a research questionnaire. Body weight and height were measured and body mass index computed.

Results: Overall, 16,258 questionnaires were collected and analyzed during this 20 year study. There was a gradual, significant increase in OC use until the mid-1980s, from approximately 45% to 60% (P < 0.001), followed by steady rates of 58–64% since then. In contrast, the rates of smoking decreased significantly in the mid-1980s, from approximately 42% to a nadir of 22% in 1991. Since then, the rate of smoking has increased slowly but steadily, to reach a level of 35% in 1999. The OC users were more often of western (Ashkenazi) origin and came from families with more education and fewer siblings. They were more often smokers than non-OC users, and started smoking at a younger age. They had significantly lower BMI[2] than non-users. OC use was nearly identical in groups with or without multiple cardiovascular risk factors (smoking, obesity, family history).

Conclusions: Smoking and OC use are strongly associated. Other cardiovascular risk factors (smoking, obesity, family history) do not prevent OC users from smoking or smokers to use OC. We suggest that primary care physicians discourage smoking among adolescent females who wish to start using OC. A thorough medical history should be obtained to recognize all risk factors for cardiovascular disease and to provide for appropriate contraception counseling.

Background: Increased serum potassium and intraventricular hemorrhage occur frequently in preterm infants.

Objective: To retrospectively analyze data obtained on infants with severe IVH[1] in relation to blood K⁺ concentrations.

Methods: We identified all patients with severe IVH born between July 1997 and July 2000. Each patient was pair-matched with a control infant of the same gestational age (±1 week) without IVH in terms of head ultrasound findings on day 5, and whole blood K⁺ on days 3–5.

Results: There were 24 infants in each group. The IVH group had significantly lower 1 minute Apgar scores and pH and higher blood K⁺ than the control group. Blood pH and K⁺ were inversely correlated. Stepwise regression analysis, taking into account blood pH and 1 minute Apgar score, showed a correlation only between blood K⁺ and IVH status.

Conclusions: Severe IVH is significantly associated with higher blood K⁺ concentrations. A causal relationship cannot be ascertained at this point.

Background: It has been argued that arginine replacement in locus16 (Arg16) of ß₂ adrenergic receptor with glycin (Gly16) increases asthma severity, while glutamin replacement in locus 27 (Gln27) with glutamic acid (Glu27) decreases it. In addition, ethnic dependency of these polymorphisms has been described, but few studies investigated its relation to asthma severity in a non-anglosaxic population.

Objectives: To investigate non-anglosaxic ethnic influences on ß₂AR[1] polymorphisms and its correlations to asthma severity.

Methods: Sixty-six Israeli Jewish and Arab asthmatics who had near-fatal asthma and/or severe nocturnal asthma and/or steroid-dependency were investigated for genetic polymorphisms of ß₂AR and compared to matched controls. The Jewish patients included both Ashkenazi (of East European origin) and non-Ashkenazi (originating from the Middle East or North Africa). The results were compared with those of ethnically matched 113 non-asthmatic Israelis, and of non-asthmatic Anglo-Saxons described in the literature.

Results: We found no significant genetic differences between the asthmatics and their controls or between the various ethnic groups of our population. However, the prevalence of Glu27 was significantly lower in non-asthmatic Israelis compared to non-asthmatic Anglo-Saxons.

Conclusions: The genetic distribution of ß₂AR polymorphisms in severe Israeli asthmatics is not different from that of non-asthmatic Israelis and therefore its clinical impact on asthma is probably minimal.

Background: The Israeli Blood Pressure Control program was initiated to enhance the control of modifiable risk factors among high risk hypertensive patients followed by general practitioners in Israel.

Objective: To report the baseline results of the state of the treatment regarding blood pressure management, lipid and glucose control as well as obesity and smoking cessation among the patients.

Methods: Hypertensive patients were screened in 30 general practice clinics supervised by family medicine specialists seeing 1,000–5,000 patients each. Between 50 and 250 hypertensive patients were diagnosed at each participating clinic. Blood pressure levels, body mass index, lipid and glucose levels, as well as target organ damage and medications were recorded for all patients.

Results: Of the 4,948 patients registered, 2,079 were males (42%). Mean age was 64.8 ± 12. Blood pressure control was achieved in only 33.1% of total hypertensive patients. Low density lipoprotein control was achieved in 31.1% of all patients, and glucose control in only 28.5%% of diabetic patients (glucose < 126 mg/dl); 20.7% of the diabetics had glucose levels above 200 mg/dl. In this group of patients 38.9% were obese (BMI[1] >30 kg/m²). While there were more obese females than males (48.0% vs. 35.6%), no difference was found in blood pressure, lipid or glucose control between the genders.

Conclusion: Risk factor management of hypertensive patients attending general practice clinics in Israel is not optimal, especially among those with diabetes or in need of secondary prevention measures. A long-term intervention program for high risk patients in the community is needed to improve the current situation.

Background: In southern Israel, a discrepancy between a relatively high prevalence of Group B streptococcus maternal carriage (12.3%) and a very low incidence of neonatal disease (0.1/1,000 live births) has been found despite the fact that no preventive strategy has been implemented.

Objectives: To determine the risk factors for maternal carriage in order to clarify this discrepancy and further examine the different aspects of GBS[1] in southern Israel.

Methods: Cultures for GBS were obtained from 681 healthy pregnant women and relevant demographic and obstetric data were collected. The medical records of 86 neonates born to carrier women were retrospectively examined. Statistical analysis was performed using the Pearson chi-square test.

Results: Women who were not born in Israel, particularly immigrants from the former USSR, were significantly prone to carry the pathogen compared to native Israeli women (Bedouin Arabs and Jews) (P = 0.03).

Conclusions: A high GBS transmission rate is expected among immigrants who came from areas with a high prevalence of maternal carriage to one with a low incidence of neonatal disease environment and were not subject to any preventive strategy. Clinical attention should be directed to this issue throughout Israel.

Background: Hyperlipidemia is a major risk factor for coronary heart disease. Reducing low density lipoprotein-cholesterol can significantly reduce the risk of CHD[1], but many patients fail to reach the target LDL-C[2] goals due to low doses of statins or low compliance.

Objectives: To treat high risk patients with atorvastatin in order to reach LDL-C goals (either primary or secondary prevention) of the Israel Atherosclerosis Society.

Methods: In this open-label study of 3,276 patients (1,698 of whom were males, 52%), atorvastatin 10 mg was given as a first dose, with follow-up and adjustment of the dose every 6 weeks. While 1,670 patients did not receive prior hypolipidemic treatment, 1,606 were treated with other statins, fibrates or the combination of both.

Results: After 6 weeks of treatment, 70% of the patients who did not receive prior hypolipidemic medications and who needed primary prevention reached target LDL-C levels. Interestingly, a similar number of patients on prior hypolipidemic treatment reached the LDL-C goals for primary prevention. The patients treated with other statins, fibrates or both did not reach the LDL-C treatment goals. Only 34% of all patients who needed secondary prevention reached the ISA[3] LDL-C target of 100 mg/dl. Atorvastatin proved to be completely safe; only two patients had creatine kinase elevation above 500 U/L, and another six had mild CK[4] elevation (<500 U/L). None of the patients had clinical myopathy, and only one had to be withdrawn from the study.

Conclusion: Atorvastatin is a safe and effective drug that enables most patients requiring primary prevention to reach LDL-C goal levels, even with a low dose of 10 mg. Patients in need of secondary prevention usually require higher doses of statins.

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Background: Multiple factors are involved in the pathogenesis of hypertension in the obese individual.

Objective: To evaluate the role of a decrease in sympathetically mediated thermogenesis and the effect of the correlation between the plasma leptin and daily urinary nitric oxide levels on obesity-related hypertension.

Methods: We evaluated three groups: 25 obese hypertensive patients (age 45.7±1.37 years, body mass index 34.2±1.35 kg/m², systolic/diastolic blood pressure 155±2.9/105±1.3, mean arterial pressure 122±1.50 mmHg); 21 obese normotensive patients (age 39.6±1.72, BMI[1] 31.3±0.76, SBP/DBP[2] 124±2.1/85.4±1.8, MAP[3] 98.2±1.80); and 17 lean normotensive subjects (age 38.1±2.16, BMI 22.1±0.28, SBP/DBP 117±1.7/76.8±1.5, MAP 90.1±1.50). We determined basal resting metabolic rates, plasma insulin (radioimmunoassay), norepinephrine (high performance liquid chromatography) in all subjects. Thereafter, 14 obese hypertensives underwent a weight reduction diet. At weeks 6 (n=14) and 14 (n=10) of the diet the above determinations were repeated. Plasma leptin (enzyme-linked immunosorbent assay) and UNOx[4] (spectrophotometry) were assayed in 17 obese hypertensives and 17 obese normotensives, and in 19 obese hypertensives versus 11 obese normotensives, respectively.

Results: Obese hypertensive patients had significantly higher basal RMR[5] and plasma NE[6] levels. Insulin levels were lower in the lean group, with no difference between the hypertensive and normotensive obese groups. At weeks 6 and 14, BMI was significantly lower, as were insulin and NE levels. RMR decreased to values of normotensive subjects. MAP normalized but remained significantly higher than that of obese normotensives. Leptin blood levels and the leptin/UNOx ratio were significantly higher in the obese hypertensive compared to the obese normotensive patients. Both these parameters were strongly correlated to BMI, MAP⁵, RMR, and plasma NE and insulin .Obese hypertensive patients excreted less urinary NO metabolites. A strong correlation was found between MAP and the leptin/UNOx ratio.  

Conclusions: A reduction of sympathetically mediated thermogenesis, as reflected by RMR, results in normalization of obesity-related hypertension. In contrast, insulin does not seem to play a major role in the pathogenesis of hypertension associated with obesity. Increased leptin levels in conjunction with decreased NO production in the presence of enhanced sympathetic activity may contribute to blood pressure elevation in the obese.

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[1] BMI = body mass index

[2] SBP/DBP = systolic blood pressure/diastolic blood pressure

[3] MAP = mean arterial pressure

[4] UNOx = urinary nitric oxide

[5] RMR – resting metabolic rate

[6] NE = norepinephrine

Background: Case-control and prospective studies indicate that an elevated plasma homocysteine level is a powerful risk factor for atherosclerotic vascular diseases. Certain medications can induce hyperhomocystinemia, such as methotrexate, trimethoprim and anti-epileptic drugs. There are few reports indicating an interaction between lipid-lowering drugs (cholestyramine and niacin) and homocysteine. Recently, an interaction was shown between fenofibrate and benzafibrates (a fibric acid derivative) and homocysteine plasma levels.

Objectives: To evaluate the effects of different fibrates on plasma homocysteine levels and to measure the reversibility of this effect.

Methods and Results: We investigated the effects of ciprofibrate and bezafibrate on homocysteine levels in patients with type IV hyperlipidemia and/or low high density lipoprotein levels. While a 57% increase in homocysteine was detected in the ciprofibrate-treated group (n=26), a 17% reduction n homocysteine was detected in the group treated with bezafibrate (n=12). The increase in homocysteine in the ciprofibrate-treated group was sustained for the 12 weeks of treatment and was partially reversible after 6 weeks of discontinuing the ciprofibrate therapy.

Conclusions: These results indicate that an increase In plasma homocysteine levels following administration of flbrates is not a class effect, at least in its magnitude. Moreover, it is reversible upon discontinuation of the treatment.