Israel Medical Association Journal

Objective: To provide comparative information in an international context on the level of outpatient drug expenditures in Israel, both total and those publicly financed, and to analyze how these have changed with time during the last decade.

Methods: Using definitions of the OECD (Organization of Economic Cooperation and Development), internationally comparable data on total expenditure and public expenditure on medicines in Israel are provided. The Israeli estimates are based on data from the Ministry of Health audited reports of financial activities of the health management organizations and from the family expenditure surveys carried out by the Central Bureau of Statistics. Per capita total and public expenditures in Israel are analyzed over time, as are their share of national expenditure on health and of gross domestic product. Israel expenditures are then compared with those for individual member countries of the OECD, as well as a 21 country average, from 1992 to 2002.

Results: Analysis of the Israeli expenditure data shows a considerable reduction in growth of per capita total and public expenditures on medicines since 1997. Growth in the share of total drug expenditure of NEH[1] and of GDP[2] has also been constrained since 1997. In an international context, per capita expenditure on medicines in Israel, particularly what is publicly financed, is one of the lowest. Furthermore, its share of NEH and GDP is also very low compared to other countries. This substantive gap in spending on medicines between Israel and other countries has increased since 1997.

Conclusions: Israel, a medium-income country with a lower than average level of expenditure on health compared to OECD countries, has a particularly low level of expenditure on medicines. Whereas the share of health expenditure of GDP in Israel is similar to the international average, the share of drug expenditure of GDP is well below the average. In addition to structural and longer-term factors contributing to Israel's low per capita spending on medicines, such as the young population and the apparently low level of actual prices paid by most institutional purchasers, recent years are witness to the growing impact of National Health Insurance budgetary pressures on HMOs[3] as well as continual increases in prescription cost sharing by patients. The impact is felt both on the demand side (higher co-payments, administrative and prescribing restrictions) and perhaps more crucially on the supply side (price competition, mainly from generics). Substantial extra public funding for the addition of new drugs to the NHI[4] basket in recent years has had no overall impact on these longer-term spending patterns.

Objectives: To assess the effect of a vaginal ring delivering estradiol and progesterone in postmenopausal women and to determine whether continuous administration can relieve climacteric symptoms, produce an acceptable pattern of vaginal bleeding and control endometrial proliferation.

Methods: Twenty-nine postmenopausal women with an intact uterus were studied. All had climacteric symptoms. The vaginal rings contained 0.36 g estradiol and either 3.6 g progesterone (high dose progesterone) or 1.8 g (low dose progesterone), and were kept in place for 4–6 months. Serum progesterone, estradiol and estrone were measured and endometrial thickness determined. All women kept a daily diary of bleeding/spotting and completed a questionnaire on climacteric symptoms at monthly intervals. The low dose progesterone group comprised 14 women and the high dose progesterone group 15 women.

Results: A total of 18 patients (9 in each group) completed the study. Mean levels of estradiol, estrone and progesterone were at their peak after 2 to 4 weeks. All rings were effective in alleviating vasomotor symptoms, although there was evidence of the "escape from effect" in month 6. Endometrial thickness increased in 6 of the 29 women but biopsy in each case showed no evidence of hyperplasia. Of the 18 women who completed the study, 5 had amenorrhea throughout, 7 had amenorrhea after 3 months, and the remainder had one or two bleeding episodes after 3 months. Therapy was discontinued in 11 women.

Conclusions: A vaginal ring delivering estradiol and progesterone controlled climacteric symptoms, prevented endometrial proliferation, and provided an acceptable bleeding pattern. It should be viewed as a promising alternative for short-term estrogen-progesterone therapy.

Objectives: To compare the outcomes of two groups of CICF[1] patients who underwent two different treatment protocols.

Methods: The study cohort included 72 infants treated in our hospital from August 1998 to December 2002. Group 1 comprised 40 infants (61 clubfeet) who were treated by a traditional method (a modification of the Kite and Lovell technique), and group 2 consisted of 32 infants (48 clubfeet) who were treated with the Ponseti technique. Both groups were similar in age, gender and severity of the deformity (Dimeglio scoring system)

Results: After an average follow-up of 54.9 months (range 44–68), 35 (57%) clubfeet in group 1 required surgical intervention and 27 (44%) clubfeet had a residual deformity at last follow-up. In the Ponseti group, 45 (94%) clubfeet were fully corrected at last follow-up (average 29.2 months, range 16–45) while 3 (6%) clubfeet had residual deformity and required surgery. Tendo-Achilles tenotomy was performed with no complications in 47 clubfeet (in group 2) at an average age of 2.4 months (range 2–4 months).

Conclusions: Even after a relatively short follow‑up period, our success rate with the Ponseti approach already appears to be significantly higher and to bear fewer complications than the traditional treatment, in agreement with the results published by other medical centers. We now endorse the Ponseti technique of conservative manipulative treatment for congenital idiopathic clubfoot in our department.

Objective: To investigate gender differences in the baseline characteristics, clinical presentation, treatment and prognosis of women with unstable angina.

Method: Data were collected prospectively as part of the Acute Coronary Syndromes Israeli Survey in 2000 at Soroka University Medical Center. In-hospital management and 2 year follow-up were monitored for 226 consecutive patients with unstable angina admitted to our medical center during February and March 2000.

Results: Women were older (71 ± 12 vs. 66 ± 12, P = 0.006), more diabetic (41.3% vs. 34.5%, not significant) and hypertensive (76.3% vs. 64.6%, P = 0.07). Women presented more often with atypical chest pain (18.8% vs. 7.5%, P = 0.038). Heparin, aspirin and angiotensin-converting enzyme inhibitor were equally delivered, but more beta-blockers were administered to women (88.5% vs. 75.7%, P = 0.02) and more statins to men (48.1% vs. 35.4%, P = 0.07). Angiography rates were similar (17.7% vs. 19.6%). Similar management was documented during the 2 year follow-up. Re-hospitalization rates were similar (53.3% of women and 63.7% of men, NS). Men had a tendency to develop acute myocardial infarction more often (9.6% vs. 2.7%, P = 0.06) and to develop peripheral vascular disease (3.7% vs. 0%, P = 0.09), and they had a non-significant higher rate of coronary artery bypass graft (6.7% vs. 1.3%, P = 0.08). No gender difference was found in angiography (14.7% of women vs. 16.3% of men) or percutaneous intervention (13% vs. 16.7%). At 2 years there was no gender-related difference in mortality (13.3% of women vs. 16.3% of men, NS). Kaplan-Meier analysis for event-free survival after 2 years showed no gender difference in survival. Multi-regression analysis showed that gender was not a prognostic factor for survival.

Conclusions. We found no major difference in the management of men and women with unstable angina. Although men showed a tendency to suffer more major cardiac events, their 2 year prognosis was the same as for women.

Background: Repaglinide, a new insulin secretagogue, is purported to be as effective as sulphonylurea but is less hypoglycemic-prone.

Objectives: To assess the efficacy of repaglinide and its proclivity for hypoglycemia in a post-marketing study.

Methods: The study group comprised 688 patients, aged 26–95 years, clinically diagnosed with non-insulin-dependent type 2 diabetes. The patients were divided into three groups based on previous therapy: a) sulphonylurea-treated (group 1, n=132); b) metformin with or without sulphonylurea where sulphonylurea was replaced with repaglinide. (group 2, n=302); and c) lifestyle modification alone (drug-naïve) (group 3, n=254). At initiation of the study, all patients were transferred from their current treatment to repaglinide. Only patients in group 2, with combined sulphonylurea plus metformin, continued with metformin plus repaglinide. Fasting blood sugar, hemoglobin A1c and weight were measured at study entry and 4–8 weeks following repaglinide therapy. A questionnaire documented the number of meals daily and the presence of eating from fear of hypoglycemia.

Results: The fasting blood sugar level of the entire cohort dropped from 191 ± 2.4 to 155 ± 2.0 mg/dl (P < 0.0001); HbA1c from 8.8 ± 0.1 to 7.7 ± 0.1% (P < 0.0001). The drop of HbA1c in groups 1, 2 and 3 respectively were: 1.04 ± 0.22% (P < 0.0001), 1.14 ± 0.24% (P < 0.0001), and 1.51 ± 0.31% (P = 0.0137). Weight dropped from 81 ± 0.7 to 80.2 ± 0.7 kg (P < 0.0001), and eating from fear of hypoglycemia from 157 to 97 (P < 0.001). The daily number of meals decreased from 2.9 ± 0.4 to 2.4 ± 0.4 (P < 0.001). No serious adverse reactions occurred during the study.

Conclusions: Repaglinide is an effective oral hypoglycemic agent taken either as monotherapy or combination therapy. There is less eating to avoid hypoglycemia, fewer meals consumed, and weight loss.

Background: Alteration of innate and acquired immunity can play a role in the mechanism involved in the development of dementia. Epidemiologic studies indicate that the use of non-steroidal anti-inflammatory drugs can delay the onset or slow progression of Alzheimer disease.

Objectives: To determine whether the use of NSAIDs[1] is associated with natural killer activity alteration in AD[2] and multi-infarct vascular dementia patients, as compared with non-demented elderly and healthy young people.

Methods: In this prospective open study four groups of subjects (AD, VD[3], non-demented elderly, and healthy young people) were treated with an NSAID drug (rofecoxib 12.5 mg/day or ibuprofen 400 mg twice daily) for 7 days. Natural killer cell cytotoxicity was measured after flow cytometry analysis before and after treatment.

Results: Of the 49 subjects studied, 15 had a diagnosis of AD (3 men, 12 women; mean age 83.5 ± 8.1 years), 15 had a diagnosis of multi-infarct VD (7 men, 8 women; mean age 75.5 ± 8.4), 13 were non-demented elderly (1 man, 12 women; mean age 80.2 ± 7.2), and 6 were healthy young volunteers (3 men, 3 women; mean age 36.8 ± 4.4). While all examined subjects showed decreased NK[4] cell cytotoxicity after treatment, this decrease was most prominent and statistically significant in elderly patients suffering from vascular dementia –  from an average of 30.5 ± 11.8% before treatment to 22.5 ± 16% after treatment (P = 0.04). The decrease in NK cell cytotoxicity was only moderate and not statistically significant in all other elderly and young subjects. Young healthy volunteers exhibited a significantly higher total NK cytotoxicity before and after treatment compared to all age groups (P < 0.001).

Conclusion: These findings suggest that NSAIDs decrease NK activity in vascular dementia patients. Our findings also suggest that natural killer activity alteration cannot explain the ability of anti-inflammatory drugs to delay the onset or slow the progression of AD.

Background: Repaglinide, a new insulin secretagogue, is purported to be as effective as sulphonylurea but is less hypoglycemic-prone.

Objectives: To assess the efficacy of repaglinide and its proclivity for hypoglycemia in a post-marketing study.

Methods: The study group comprised 688 patients, aged 26–95 years, clinically diagnosed with non-insulin-dependent type 2 diabetes. The patients were divided into three groups based on previous therapy: a) sulphonylurea-treated (group 1, n=132); b) metformin with or without sulphonylurea where sulphonylurea was replaced with repaglinide. (group 2, n=302); and c) lifestyle modification alone (drug-naïve) (group 3, n=254). At initiation of the study, all patients were transferred from their current treatment to repaglinide. Only patients in group 2, with combined sulphonylurea plus metformin, continued with metformin plus repaglinide. Fasting blood sugar, hemoglobin A1c and weight were measured at study entry and 4–8 weeks following repaglinide therapy. A questionnaire documented the number of meals daily and the presence of eating from fear of hypoglycemia.

Results: The fasting blood sugar level of the entire cohort dropped from 191 ± 2.4 to 155 ± 2.0 mg/dl (P < 0.0001); HbA1c from 8.8 ± 0.1 to 7.7 ± 0.1% (P < 0.0001). The drop of HbA1c in groups 1, 2 and 3 respectively were: 1.04 ± 0.22% (P < 0.0001), 1.14 ± 0.24% (P < 0.0001), and 1.51 ± 0.31% (P = 0.0137). Weight dropped from 81 ± 0.7 to 80.2 ± 0.7 kg (P < 0.0001), and eating from fear of hypoglycemia from 157 to 97 (P < 0.001). The daily number of meals decreased from 2.9 ± 0.4 to 2.4 ± 0.4 (P < 0.001). No serious adverse reactions occurred during the study.

Conclusions: Repaglinide is an effective oral hypoglycemic agent taken either as monotherapy or combination therapy. There is less eating to avoid hypoglycemia, fewer meals consumed, and weight loss.
 

Background: Alteration of innate and acquired immunity can play a role in the mechanism involved in the development of dementia. Epidemiologic studies indicate that the use of non-steroidal anti-inflammatory drugs can delay the onset or slow progression of Alzheimer disease.

Objectives: To determine whether the use of NSAIDs[1] is associated with natural killer activity alteration in AD[2] and multi-infarct vascular dementia patients, as compared with non-demented elderly and healthy young people.

Methods: In this prospective open study four groups of subjects (AD, VD[3], non-demented elderly, and healthy young people) were treated with an NSAID drug (rofecoxib 12.5 mg/day or ibuprofen 400 mg twice daily) for 7 days. Natural killer cell cytotoxicity was measured after flow cytometry analysis before and after treatment.

Results: Of the 49 subjects studied, 15 had a diagnosis of AD (3 men, 12 women; mean age 83.5 ± 8.1 years), 15 had a diagnosis of multi-infarct VD (7 men, 8 women; mean age 75.5 ± 8.4), 13 were non-demented elderly (1 man, 12 women; mean age 80.2 ± 7.2), and 6 were healthy young volunteers (3 men, 3 women; mean age 36.8 ± 4.4). While all examined subjects showed decreased NK[4] cell cytotoxicity after treatment, this decrease was most prominent and statistically significant in elderly patients suffering from vascular dementia –  from an average of 30.5 ± 11.8% before treatment to 22.5 ± 16% after treatment (P = 0.04). The decrease in NK cell cytotoxicity was only moderate and not statistically significant in all other elderly and young subjects. Young healthy volunteers exhibited a significantly higher total NK cytotoxicity before and after treatment compared to all age groups (P < 0.001).

Conclusion: These findings suggest that NSAIDs decrease NK activity in vascular dementia patients. Our findings also suggest that natural killer activity alteration cannot explain the ability of anti-inflammatory drugs to delay the onset or slow the progression of AD.

Objective: To investigate the effect of the Dead Sea environment (climatotherapy) on the signs, symptoms and clinical course of chronic uveitis.

Methods: Fifty-five patients with chronic uveitis were examined at the beginning and end of a 3–4 week stay at the Dead Sea region and on repeat visits to the region. Study data included demographic information, medical history, etiology, diagnosis, medication, and a complete ophthalmic examination.

Results: Statistically significant improvements were seen between the two examinations within each visit in four parameters (negative values indicate improvement): a) visual acuity for near and far: Jaeger (‑1.18 ± 0.28, P < 0.0001) and best corrected visual acuity (‑0.08 ± 0.02, P < 0.0001); b) anterior chamber flare (-0.18 ± 0.06, P < 0.01); c) anterior chamber cells (-0.16 ± 0.05), P < 0.001); and d) vitreous cells (-0.15 ± 0.09, P < 0.05). There was a significant mean improvement during visits to the Dead Sea area and a slight dissipation of the effect during the intervals between visits. Sixty-four percent of the patients reported that they required less medication and had fewer and milder attacks of uveitis following the visits.

Conclusions: The results of this study provide evidence of short- and possibly long-term improvement in the signs and symptoms of uveitis following exposure to the Dead Sea environment.

Background: Ultrasound is useful in detecting acromioclavicular pathologies in cases of trauma, inflammations and degenerative changes.

Objectives: To describe the sonographic findings of the acromioclavicular joint pathology in patients with anterior shoulder pain.

Methods: Sonographic examination of the ACJ[1] was used to examine 30 adults with anterior shoulder pain. As a control group we studied 30 asymptomatic patients and compared the findings to plain radiographs of the symptomatic group.

Results: The pathologic findings consisted of swelling of the joints, bone irregularities, widening and/or narrowing of the ACJ, soft tissue cyst formation, excessive fluid collection, and calcification. All these signs represent degenerative changes compatible with early osteoarthritis. We encountered one case of septic arthritis that required joint aspiration and antibiotic treatment.

Conclusions: It is our belief that ultrasonography should be used routinely in cases of anterior shoulder pain since it demonstrates various pathologies undetected by plain radiographs.