Amos M. Yinnon MD, Yitzhack Skorohod MD, Yechiel Schlesinger MD and Alan Greenberg BPharm MRPharmS
Background: Cefuroxime is a second-generation cephalosporin antibiotic used widely for the treatment of various infections.
Objectives: To assess the appropriateness of cefuroxime usage as well as the long-term impact of re-feeding the results to prescribing physicians.
Methods: Drug utilization evaluation involved three data-collecting periods, each comprising 6 weeks, during which all patients receiving cefuroxime were evaluated. Results of phase I were distributed to all physicians in a newsletter and departmental lectures; phase II was announced and conducted 6 months later. An identical phase III was unannounced and conducted one year after phase II. The study included all patients receiving cefuroxime during the three phases. The main outcome measure was appropriateness of initiation, and continuation beyond 3 days, of empirical treatment. Appropriateness was determined according to a prepared list of indications based on the literature and the hospital's protocols.
Results: Cefuroxime was initiated appropriately in 104 of 134 patients (78%) in phase I, in 85 of 100 (85%) in phase II, and in 93 of 100 (93%) in phase III (P<0.001). Cefuroxime was continued appropriately after 3 days in 58/134 (43%), 57/100 (57%) and 70/100 (70%) respectively (P<0.001). The total number of appropriate treatment days out of all treatment days increased from 516 of 635 (81%) in phase I, to 450 of 510 (88%) in phase II, to 485 of 509 (95%) in phase III (P<0.001). The principal reason for cefuroxime usage was community-acquired respiratory tract infection.
Conclusion: Drug utilization evaluation may provide valuable data on the usage of a particular drug. This information, once re-fed to physicians, may improve utilization of the particular drug. This positive effect may be prolonged beyond the immediate period of observation.
Tamy Shohat MD, Manfred S. Green MD PhD, Orly Nakar MD, Ami Ballin MD, Poriya Duvdevani PhD, Avital Cohen MD and Mordechai Shohat MD
Background: In trials comparing different formulations of measles vaccine, excess non-specific mortality occurred in female children who received high titer vaccine. These findings suggest a gender-specific effect of measles vaccine.
Objectives: To determine whether gender differences exist in the rates of adverse reactions and morbidity in the month following immunization with measles-containing vaccine, and to evaluate whether there is a gender-specific association between the humoral immune response to measles vaccination and post-vaccination morbidity.
Methods: Parents completed questionnaires on the health status of 755 infants aged 15-20 months, during the month preceding and the month following the measles-mumps-rubella vaccination. Blood samples were tested for measles antibody titers in a subsample of 237 infants.
Results: After controlling background morbidity in the infants, the relative risk of fever and rash following vaccination was 2.35 in females and 1.36 in males. The geometric mean antibody titers against measles were similar in both sexes and there was no significant association between antibody titer and post-vaccination morbidity in either sex.
Conclusions: Our findings demonstrate higher rates of adverse effects in females following vaccination with MMR vaccine, irrespective of the humoral response. This study emphasizes the need to consider possible gender differences when evaluating new vaccines.
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MMR= measles-mumps-rubella
Yael Avrahami-Heller MD [DTB], Dani Cohen MD, Noam Orr MD, Raphael Slepon MD,Israel Ashkenazi MD, Yehuda L. Danon MD
Background: Chickenpox is a highly contagious childhood infection caused by varicella zoster virus, a virus of the herpes family. Although a mild and self-limiting disease in otherwise healthy children, chickenpox can be a complicated and even life-threatening disease in adults, pregnant women and immunosuppressed individuals. Among infants whose mothers had varicella during the first trimester of pregnancy, 2-3% will develop a congenital VZV syndrome that includes a combination of scarring, limb deformation, central nervous system impairment and ocular injury. In 1974, a live attenuated virus vaccine against VZV was developed in Japan and has been thoroughly tested for safety, efficacy and long-term effects. In March 1995 the vaccine was licensed in the U.S. for use in healthy children only.
Objectives: To determine the rate of immunity to VZV in young Israeli adults.
Methods: On the assumption that a randomly picked sample of 18-year-old army recruits in Israel is representative of the general Jewish population, 900 sera samples were taken for 3 years (1985,1988,1992). The sera were analyzed for IgG to VZV with a commercial ELISA kit using microwells coated with VZV antigens.
Results: A total of 98% of the samples tested positive for VZV antibodies. The difference in serologic values between the recruitment years was not statistically significant.
Conclusion: The majority of the Israeli population reaches adulthood already immunized against VZV, with immigrants having slightly lower immunity rates. Nonetheless, a few dozen cases of chickenpox are diagnosed in the IDF annually. These data should be taken into account when a vaccination program is devised. Should such a program be implemented, it would be interesting to repeat the serosurvey for comparison. A shift in the peak occurrence age might necessitate the administration of a booster vaccine at an older age.
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VZV= varicella zoster virus
IDF= Israel Defense Forces
Shlomo Vinker MD, Sasson Nakar MD, Michael A. Weingarten BM BCh, and members of the Israeli General Practice Research Network
Background: Most countries today are experiencing an accelerated pace of population aging. The management of the elderly housebound patient presents a special challenge to the family physician.
Objectives: To investigate a series of home visits to housebound patients, the therapeutic procedures used, the equipment needed, and the diagnostic conclusions reached.
Methods: The details of 379 consecutive home visits to housebound patients were recorded by 91 family doctors serving 125,000 patients in Israel.
Results: The average age of the patients was 76.1 years. The vast majority of the visits were during office hours (94%). In 24.1% it was the doctor who decided to make the home visit on his/her own initiative. The most common initial reason for a home visit was undefined general symptoms, but the doctor was usually able to arrive at a more specific diagnosis after the visit. Medications were prescribed in 59.1% of the visits, and in 23.5% the medication was administered directly by the physician. The commonest drugs used were analgesics and antibiotics. In 19.3% of visits no action at all, other than examination and counseling, was undertaken. The equipment needed included prescription pads (73%), a stethoscope (81%), sphygmomanometer (74.9%), and otoscope/torch (30.6%). Only 15% of visits resulted in referral to hospital.
Conclusions: Home visits to housebound patients serve as a support to caregivers, provide diagnostic information, and help the family with the decision as to when hospitalization is appropriate. The specific medical cause for the patient being housebound had little effect on the process of home visiting.
Joseph Meyerovitch MD, Trevor Waner BVSc PhD, Joseph Sack MD, Juri Kopolovic MD and Joshua Shemer MD
Background: Despite current treatment protocols, the long-term complications of insulin-dependent diabetes mellitus have prompted the investigation of strategies for the prevention of IDDM.
Objectives: To investigate the effect of oral vanadate in reducing diabetes type I in non-obese diabetic mice.
Methods: Sodium metavanadate, 3.92 mmol/L, was added to the drinking water of 8-week-old female NOD mice. Blood glucose levels, water consumption and body weight were measured, and the end point of the study was judged by the appearance of hyperglycemia in the mice.
Results: Treatment with vanadate did not significantly reduce the incidence of type I diabetes as compared to the control group. However, oral vanadate therapy significantly reduced the blood glucose levels after the fourth week of treatment compared to the control group (3.83±10.67 vs. 4.44±10.83 mmol/L, P<0.03). There was a consistent and significant increase in body weight of the vanadate-treated pre-diabetic NOD mice compared to the controls. Diabetic mice treated with vanadate had significantly lower levels of serum insulin as compared to control diabetic mice (104±27 vs. 151±36 mol/L, P<0.03). Histologically, no significant differences were found in inflammatory response of the islets of Langerhans between the control and treated groups.
Conclusions: This study suggests that the post-receptor insulin-like effect induced by vanadate is not sufficient to prevent the development of diabetes and insulitis in pre-diabetic NOD mice.
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IDDM= insulin-dependent diabetes mellitus
NOD= non-obese diabetic
Menahem Fainaru MD and Zehava Schafer MsC
Background: Dyslipidemia and obesity serve as risk factors for the development of atherosclerotic cardiovascular disease. Fasting is sometimes recommended for treating these conditions. This study was undertaken to try to resolve conflicting results reported in the literature.
Objectives: To study the effect of fasting (0 calories, with free intake of fluids) for 3-5 days on plasma concentration of triglyceride, cholesterol and apolipoprotein B.
Methods: Physicians, about to begin a hunger strike, were divided into four groups: normolipidemic non-obese men (group 1), two moderately obese men and two men with type IV hyperlipidemia (group 2), healthy non-obese women (group 3), and healthy non-obese women on oral contraceptives (group 4). Adherence to fasting was monitored daily by detailed interviews, loss of weight, drop in plasma glucose, presence of ketonuria, progressive rise in serum creatinine and uric acid, and decrease in plasma pH. We monitored their serum glucose, electrolytes, liver function, lipids, lipoproteins and apolipoprotein B on days 0, 3, and 5.
Results: Physicians who adhered to complete fasting lost more than 1.5% of their body weight after 3 days of fasting (n=12), and more than 3.2% at 5 days (n=5). All non-obese normolipidemic males and females (groups 1 and 3) showed an increase in plasma triglyceride (by 28-162%) and very low density lipoprotein cholesterol (by 22-316%) after 3 days of fasting. The obese and hyperlipidemic men (group 2) showed a decrease of 17-63% in their VLDL cholesterol, and the women on oral contraceptives (group 4) showed a 20% decrease in their plasma triglyceride on day 3. Low density lipoprotein cholesterol increased by 13% in group 2, decreased by 7.3% in group 4, and remained unchanged in group 1 and 3. Apolipoprotein B level correlated well with LDL cholesterol in all groups. High density lipoprotein cholesterol changes were inconsistent.
Conclusions: These results help to explain and reconcile previous published reports. The metabolic background of the individual together with the amount of energy consumed affect the behavior of plasma lipids and lipoproteins levels during fasting.
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VLDL= very low density lipoprotein
LDL= low density lipoprotein
Ronen Rub, MD, David Margel, MD, Dror Soffer MD and Yoram Kluger, MD
Background: The course and outcome of appendicitis in the elderly differs from that of the general population. The rates of perforated appendices, error in diagnosis, postoperative complications and mortality may be related to the time lapse between onset of symptoms and admission, and hence delay in surgery.
Objectives: To evaluate if these factors have improved in recent years.
Methods: A retrospective study was carried out of all 61 patients over age 60 who underwent appendectomies in a major metropolitan hospital during 1988-98.
Results: We found that most patients had appendectomies within the first 24 hours of admission and within 3 days of symptoms. Rate of perforation was 43%, error 5.6%, morbidity 41%, and mortality 3.2%.
Conclusions: The high rate of appendix perforation in the elderly is not due to delay. The literature reveals little improvement in the statistics of the disease over the last five decades, despite advances in imaging and surgical technique. This may be explained by the increasing inclusion of octogenarian patients.
Anabel Aharon-Maor, MD and Yehuda Shoenfeld, MD
Michael David, MD, Dov Efron, PhD, Emmilia Hodak, MD and Zvi Even-Paz
by Zaher S. Azzam, MD and Jacob I. Sznajder, MD
Israel Hodish, MD, David Ezra, MD, Hanan Gur, MD, Rephael Strugo, MD and David Olchovsky, MD
Orna Geyer, MD, Meira Neufelder, MD, Adi Michaeli-Cohen, MD, Moshe Lazar, MD, Sigal Sadetzki, MD and Baruch Modan, MD
Elias Toubi, MD, Johana E. Naschitz, MD, Aharon Kessel, MD and Milo Fradis, MD
Michael Heim, MB CHB, Elinor Goshen, MD, Aharon Chechick, MD, Ilan Cohen, MD and Morris Azaria, MD