The Israeli Pharmaceutical Market

Segev Shani, Joshua Shemer

Pharmaceutical Policy and Economics Unit, Israeli Center for Health Technology Assessment in Health Care, Gertner Institute for Epidemiology and Health Policy Research, Tel Hashomer and Sackler Faculty of Medicine, Tel Aviv University

The pharmaceutical market in Israel has undergone many major changes over the past 2 years. We detail measures taken with regard to drug prices and utilization, from 1992 until 1995, when the National Health Insurance Law was implemented. This provides an information base for marketing and dispensing of drugs, economic planning in the public health system, and for physicians and pharmacists in clinical practice.

The national expenditure on pharmaceuticals in 1994 was 9.4% of the annual national health expenditure. From this fact, and the number of registered drugs and the number of clinical trials conducted, it appears that our pharmaceutical market is quite diversified and well developed compared to other markets in the western world. This size advantage enables our sick funds to purchase drugs at much lower prices than the private sector.

EBV-Related Post-Transplantation Lymphoproliferative Disorder

D. Doron, O. Papo, O. Portnoy, E. Granot

Depts. of Pediatrics, Pathology, and Radiology, Hadassah University Hospital, Jerusalem

We describe a 4.5-year-old girl in whom post transplantation lymphoproliferative disorder was diagnosed 1 year after liver transplantation. She ran a complicated course with multiple organ involvement: respiratory failure which required mechanical ventilation, renal failure, bone marrow depression and severe protein-losing enteropathy.

Severe Heat Stroke in an Intensive Care Unit

Amir Halkin, Dina Lev, Oded Szold, Philip Bidermann, Sarah Bulocnic, Pinchas Halpern, Patrick Sorkine

Depts. of Medicine and Surgery, and Intensive Care Unit, Tel Aviv Medical Center

During the August 1998 heat wave in Tel Aviv we admitted many patients for acute heat-related illness; 6 had severe heat stroke and were admitted in critical condition. We describe their clinical courses during the first 5 days of hospitalization, including response to treatment and implications for future management of this disorder.

The mean APACHE II score of the 6 was 30±3.5 and mean Glasgow Coma Scale rating 3.5±0.5; they were in hypovolemic shock and respiratory failure, necessitating mechanical ventilation. Despite early effective therapy (core temperature in all was reduced to less than 398C in less than 1 hour), there was 1 death (mortality 15%) and 4 required further intensive care for life-threatening multiple organ failure.

During severe heat waves a significant number of referrals for acute heat-related illness must be anticipated, possibly overwhelming admission capacity of regional intensive-care units. Severe heat stroke complicated by multi-organ failure is not necessarily related to prior physical activity. Although important in determining prognosis, early treatment does not prevent severe complications. Mechanisms regulating body heat may remain disturbed for days following early treatment and apparent stabilization, mandating continued hospitalization.

The New Family Physician

Eliezer Kitai, Avraham Sandiuk, Michael Weingarten, Shlomo Vinker

Dept. of Family Medicine, Rabin Medical Center (Beilinson Campus), Petah Tikva and Sackler School of Medicine, Tel Aviv University

The content of all consultations of a family physician during the first 2 months in a new practice and again in the same 2 months, 2 years later were analyzed. The workload did not change between the 2 periods, but in the first period there were relatively more men over the age of 60 years, and a more marked predominance of women in the 45-59 year age-group.

There were more follow-ups of pre-existing conditions during the first period, but in both periods the main reason for visits was an acute condition; a quarter of visits required only simple counseling without further investigation or prescribing of medication. During the first period 9% of visits were for the explicit purpose of getting to know the new physician, usually by women.

Thus the initial period in a new practice is not excessively burdensome, but involves seeing a number of patients who come either simply to get to know the new doctor, or to present non-chronic problems without expectation of further investigation.

Prevalence of Medical Complaints in the Community-Dwelling Elderly

J. Gindin, M. Geitzn, M. Dushenat, H. Siboni, D. Goldstein, Z. Shapira, N. Konstantin, A. Wurm, A. Goldsmid, E. Hay-Am

Geriatric Institute of Education and Research, Kaplan Medical Center, Rehovot; Pharmacology Dept., Kupat Holim Klalit, Tel Aviv and Central District; and Kupat Holim Klalit, Rishon LeZion

We assessed the prevalence of self-reported medical complaints among the community-dwelling elderly receiving regular medication, and determined associations between health and sociodemographic variables, and the prevalence of complaints.

The study included 170 patients, 60-90 years of age, living at home. Participants were recruited from the 3 main primary care clinics in Rishon LeZion. All were receiving chronic medication and were followed-up utilizing a long-term medication card. Data were gathered in interviews held in patients' homes using a structured questionnaire which included sociodemographics, diseases and medication, mental state assessment by Katzman's score, and a list of 15 medical complaints common among the aged. Relations to age, gender, education, living arrangements, number of diseases and number of medications per patient were determined.

Mean age of participants was 73.2±6.0 years and they suffered an average of 4.07±2.16 diseases and took 5.10±2.83 types of drugs. The most prevalent complaints were: weakness and fatigue (65.0%), agitation and restlessness (56.4%), dry mouth (45.6%), constipation (43.6%) and dizziness (43.2%). The number of diseases, gender, education and age had the strongest associations with the prevalence of specific complaints, as well as their total number. The association between number of medications and mean number of complaints was of borderline significance.

Limited Percutaneous Surgical Drainage in Severe Neonatal Necrotizing Enterocolitis in Low Birth Weight Prematures

Robert Finaly, Zahavi Cohen, Vadim Kapuller, Agneta Golan, Edna Kurtzbart, Abraham Mares

Depts. of Pediatric Surgery and Neonatology, Soroka Medical Center and Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer Sheba

The usual treatment of complicated neonatal necrotizing enterocolitis (NEC) is resection of the necrotic bowel, lavage of the peritoneal cavity and diversion enterostomy. Low-birth-weight premature neonates with this condition are in special danger if general anesthesia and full exploratory surgery is contemplated.

A relatively simple alternate procedure is percutaneous insertion under local anesthesia of a soft abdominal drain, most often in the right lower quadrant. The procedure is done in the neonatal intensive care unit without moving the whole set-up to the operating room.

4 such cases have been treated within the past year. 3 were discharged home as they did not require additional surgical treatment, not having developed intestinal stenosis or obstruction. 1 recovered from the acute episode, but succumbed to a severe intraventricular hemorrhage and respiratory failure 7 days after the procedure.

Our limited but most gratifying experience, in addition to similar experience of others, encourages us to recommend this simple surgical approach in the very sick low-birth-weight premature with fulminant NEC.

Neuropsychiatric Side Effects of Malarial Prophylaxis with Mefloquine

T. Minei-Rachmilewitz

Dept. of Psychiatry, Hadassah Hospital Ein Karem, Jerusalem

There has been an increased incidence of malaria among Europeans returning from Africa and Asia. The relatively new antimalarial mefloquine (Lariam) has become extremely popular due to its efficacy in treatinthe wide-spread chloroquine-resistant Plasmodium falciparum.

Mefloquine is used both for prophylaxis and treatment of malaria and is relatively well tolerated. However, since introduced in 1985, there have been over 100 reports of severe neurologic and psychiatric adverse effects associated with its use, including acute psychosis, affective disorders, acute confusional states and seizures.

We describe a 39-year-old woman who developed acute psychosis after being given mefloquine prophylaxis. Adverse effects occur more often after therapeutic rather than prophylactic use, and those with a history of seizures or psychiatric illness are at increased risk of developing these reactions. Physicians should be aware of these possible side effects and prescribe mefloquine only when indicated.

Mesalamine-Induced Hyper- Sensitivity Pneumonitis

D. Zamir, J. Weizman, C. Zamir, Z. Fireman, P. Weiner

Dept. of Medicine A and Gastroenterology Unit, Hillel Yaffe Medical Center, Hadera and Hadera Subdistrict Health Office

A 23-year-old woman was admitted with a history of 2 weeks of cough, fever and bilateral lung infiltrates. She had been diagnosed 2 months before as having ulcerative proctitis and was treated with mesalamine, which induced a full remission, but 3 antibiotic regimens failed to improve her lung disease.

Since computerized tomography revealed bilateral peripheral lung infiltrates and her eosinophile count was elevated, the diagnosis of drug-induced eosinophilic pneumonia was suggested. Mesalamine and antibiotics were stopped and oral corticosteroids begun. She became almost asymptomatic a week after mesalamine withdrawal, and the x-ray became normal.

Sonographic Demonstration of a Levonorgestrel-Releasing LUD

Yaron Zalel, Doron Kreizer, David Soriano, Reuven Achiron

Ultrasound Unit, Obstetrics and Gynecologic Dept., Sheba Medical Center, Tel Hashomer and Sackler School of Medicine, Tel Aviv University

Mirena, a new intra-uterine device (IUD) introduced in Israel during the past year, releases 20 mcg/day of levonorgestrel for 5 years. It has the advantages of reduced pregnancy rates and diminished menstrual blood loss, together with a low risk of pelvic inflammatory disease compared with current IUD's.

It has a typical sonographic appearance, differing from that of regular IUD's, which was demonstrated in all 15 women examined in this study. Its sonographic appearance includes both proximal and distal ends of the vertical arm of the device, which extend into the internal cervical os and fundal region, respectively. Acoustic shadowing between both ends defines the location of the device, which should help avoid consultations due to "lost IUD's."

Injuries Due to Falls in Urban Buses: 100 Consecutive Cases 

Ron Bachar, David Aladgem, Jacky Sarov, Patrick Sorkine, Oded Szold, Pinchas Halpern

Dept. of Emergency Medicine and Critical Care Unit, Tel Aviv-Sourasky Medical Center and Sackler Faculty of Medicine, Tel Aviv University

We reviewed the charts of 100 consecutive emergency department (ED) cases of injuries in public buses (not due to actual traffic accidents) seen during 7 months in 1995. There were 29 males and 71 females with a mean age of 55.6-21.4 years, median 60, and range 13-91. 92 were discharged home directly from the ED. 3 were admitted to general surgical wards, and 1 each to the orthopedic, medical and neurosurgical wards, while 2 soldiers were sent for observation to a military clinic.

There were 28 spinal column, 27 head and 25 chest injuries; 1 patient died. There were no significant differences in admissions during the months of the year. 58% of injuries occurred during normal working hours, with a peak incidence at about 1000 hrs. The most common cause was falling while standing, due to sudden acceleration/deceleration or sharp turns.

There are 1900 buses in Tel Aviv which carry 1.1 million passengers daily and most of which are capable of significant acceleration. A high proportion of passengers travel standing, and elderly passengers are more liable to fall when the bus accelerates, decelerates or turns. We calculate a potential national yearly bus injury toll from falls of more than 1000, which often result in significant morbidity and even mortality. A national survey is now being planned.

Prevalence of APOE 4 Allele in Israeli Ethnic Groups

O. Hilkevich, J. Chapman, B-S. Bone, A.D. Korczyn

Neurology Dept., Tel Aviv Medical Center, and Depts. of Physiology, Pharmacology and Human Genetics, Sackler Faculty of Medicine, Tel Aviv University

The 4 allele of the APOE gene, coding for apo-lipoprotein E, is the most common genetic risk factor for Alzheimer's disease and a significant risk factor for coronary atherosclerosis. There is therefore much interest in studying its frequency in different ethnic groups.

We examined its frequency in Jews originating from Libya, Buchara and Ethiopia and in Jews of Sepharadi and Ashkenazi origins. Its frequency among Ethiopian immigrants was 0.27, significantly higher than in the other groups, in which the frequency was between 0.067 and 0.10. These differences in allele frequency may serve as a basis for future studies in Israel to assess the relative contributions of genetic and environmental factors to the incidence of dementia.

Retroperitoneoscopic Lumbar Sympathectomy

D. Seror, O Zamir, D. Eimerl, H.R. Freund

Depts. of Surgery and Anesthesia, Hadassah University Hospital, Mount Scopus and Hebrew University-Hadassah Medical School, Jerusalem

We present our initial experience with retroperitoneoscopic lumbar sympathectomy in a series of 5 men aged 25-45 years. 3 suffered from ischemia of the lower limbs due to Buerger's disease, 1 had severe reflex sympathetic dystrophy and 1 had vasculitis with severe, non-healing lower leg ulcers.

The right retroperitoneal space was developed with a dissecting balloon-trocar introduced via a small lateral muscle- splitting flank incision. 2 additional 5 mm trocars were used for instrumentation and clipping. L2-L3 or L3-L4 ganglia were resected; mean operating time was 120 minutes. Only oral analgesics were needed for postoperative pain control and oral food intake was resumed the following morning. The procedure was successful in all and was without complications. Mean hospital stay was 2 days.

All patients reported significant relief of ischemia or dystrophic pain and/or improvement in trophic changes in the extremities. In the patient with leg ulcers, the largest was successfully covered with a skin graft. The retroperitoneoscopic approach to lumbar sympathectomy successfully combines the advantages of minimal invasive surgery and the reliability and effectiveness of well-established open sympathectomy.

Relapse of Sarcoidosis after Alternative Medical Treatment

Georgy Edelson, Yair Levy, Yehuda Shoenfeld

Dept. of Medicine B, Sheba Medical Center, Tel Hashomer and Sackler Faculty of Medicine, Tel Aviv University

Reference to alternative medicine frequently appears in newspaper headlines, advertisements and in articles in medical journals. The practice of alternative medicine has increased, even as the number of critical articles warning of deleterious effects have also increased. Public demand is strong and growing, but there are no clear rules as to what is not permissible, particularly when treatment is not by qualified physicians. There are still no clear indications and contra-indications for complementary (not alternative) medicine in patients with organic injuries and life-threatening conditions. However, it is obvious that in these patients complementary medicine should not be substituted for conventional therapy.

We present a 32-year-old man with sarcoidosis who discontinued conventional therapy on his own initiative and began alternative medicine (homeopathy) with subsequent deterioration in his condition. He was hospitalized for a relapse of his sarcoidosis which required large doses of corticosteroids.

Outcome in Fetuses with Increased Nuchal Translucency Thickness

Ron Maymon, Eli Dreazen, Yosi Tovbin, Zwi Weinraub, Arie Herman

Ultrasound Unit, Dept. of Obstetrics and Gynecology, Assaf Harofeh Medical Center, Zerifin and Sackler Faculty of Medicine, Tel Aviv University

Increased thickness of fetal nuchal translucency (TNT) measured at 10-14 weeks of gestation, may suggest underlying fetal chromosomal defects, structural abnormalities or genetic syndromes. We examined the relationship between increased TNT and pregnancy outcome, especially in fetuses with normal karyotypes.

1400 pregnant women underwent first trimester scanning and screening for chromosomal abnormalities and measurement of fetal TNT. 25 fetuses (2%) with increased TNT (>3 mm) were identified. 8 (30%) had an abnormal karyotype. Of these, 5 pregnancies were aborted, 3 ended in spontaneous abortions before karyotyping, and 2 were terminated, all before detailed cardiac scanning. There was a high association between increased TNT and karyotype abnormalities. The total incidence of favorable outcome in fetuses with normal chromosomal and cardiac features but enlarged TNT was 56%.

Superficial Skin Necrosis in Short Bowel Syndrome

Arie Eisenman, Rafael Enat

Dept. of Medicine B, Rambam Medical Center and Rappaport Faculty of Medicine, The Technion, Haifa

Short bowel syndrome causes a complex of symptoms due to compromise of small intestinal nutrient absorption. A 60-year-old woman underwent major resection of the small intestine due to a road accident 3 years ago. The sole manifestation of short-bowel-syndrome was superficial skin necrosis due to vitamin K deficiency. She was asymptomatic for a long time, until treatment with antibiotics further intensified initially subclinical malabsorption.

It is not clear why there had been no other symptoms and why the main impact was on the fibrinolytic system rather than the coagulation system, as is usually the case. It is recommended that patients after major resection of the small intestine be closely monitored for coagulation function if an oral antibiotic is prescribed.