Israel Medical Association Journal

Objectives: To assess the relative efficacy of clinical and laboratory methods in the diagnosis of Bordetella pertussis by patient age and immunization status.

Methods: We compared the clinical and laboratory diagnosis of B. pertussis in 87 pre-vaccinated, 78 recently vaccinated, and 75 post-vaccinated children with suspected pertussis. Serum and nasopharyngeal swabs were obtained for serology, culture and polymerase chain reaction.

Results: PCR[1] and culture identified 41% and 7% of patients with B. pertussis, respectively (P < 0.001). All positive cultures were PCR-positive. Positive PCR was less common among those recently vaccinated than among those in the pre- (P < 0.001) and post-vaccinated groups (P < 0.05). Positive culture was more common among those pre-vaccinated than among those recently vaccinated (P < 0.01). Positive tests for immunoglobulin M and A were more common among the post-vaccinated than the pre- and recently vaccinated (P < 0.001), respectively. Logistic regression analyses revealed that clinical criteria have no significant association with infection in recently and post-vaccinated children. Among the pre-vaccinated children, whoop and cough duration were associated with a positive PCR (odds ratio 7.66 and 0.5, P < 0.001). Seventy-six percent of pre-vaccinated, 39% of recently vaccinated and 40% of post-vaccinated children with positive PCR did not meet the U.S. Centers for Disease Control diagnostic criteria for B. pertussis.

Conclusions: PCR is a useful tool for pertussis diagnosis, particularly in pre-vaccinated infants. The yield of culture and serology is limited, especially among pre- and recently vaccinated children. In pre-vaccinated infants with whoop and less than 2 weeks of cough, PCR testing should be implemented promptly.

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 evaluate the extent and characteristics of CAM[1] use among cancer patients in northern Israel.

Methods: Telephone interviews were conducted with 2,176 newly registered cancer patients or their family members, at least 1 year following referral.

Results: The rates of CAM use varied significantly according to demographic characteristics and chemotherapy treatment, from 3% in the basically educated elderly group up to 69% of educated Israeli-born Jews younger than 70 years receiving chemotherapy. The overall rate of CAM use was 17%. The most influential factors determining CAM use were academic or high school education, chemotherapy treatment, Israel as country of birth, and age 41–50 years. All patients used CAM in addition to conventional therapies. Less than half of them reported it to their physicians. The most frequently used treatments were various chemical, biological, botanic and homeopathy remedies. Friends and relatives were the main recommenders of CAM. Most CAM users reported that they used CAM because they believed it “strengthens the immune system,” alleviates side effects of chemotherapy, improves quality of life and helps to overcome pain and stress, and 62% of them reported subjective beneficial effects.

Conclusions: A predicting module of CAM user patients was built, which may help physicians initiate conversations with their patients on CAM use. Expanding physicians' knowledge on CAM methods will encourage them to provide additional advice, promote the use of beneficial therapies, and inform patients about potentially harmful methods.

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[1] CAM = complementary and alternative medicine

Objectives: To test the in vitro activity of linezolid (oxazolidinone) and other antimicrobial agents against MRSA[1] isolates recovered from hospitalized patients.

Methods: We tested 150 MRSA isolates recovered from hospitalized patients. The minimal inhibitory concentration of vancomycin, teicoplanin, pristinamycin (quinupristin-dalforistin), and linezolid was determined by the Etest method. Susceptibility to other antibiotics was tested by the disk diffusion method.

Results: All isolates were sensitive to vancomycin, teicoplanin, pristinamycin, and linezolid. The MIC₉₀ was 2.0 mg/ml for vancomycin and teicoplanin (range 0.5–2.0 mg/ml and 0.125–2.0 mg/ml, respectively), and 0.5 mg/ml for pristinamycin and linezolid (range 0.125–0.75 mg/ml and 0.125–0.5 mg/m, respectively). Of the other antibiotics, fusidic acid showed the best in vitro activity, with 96.7% susceptibility, associated with trimethoprim/sulfamethoxazole (85.8%) and minocycline (84%). Penicillin was associated with the lowest susceptibility (1.3%), associated with ofloxacin (3%) and erythromycin (14%). An increase in the minimal inhibitory concentration value of vancomycin was associated with a significant decrease in resistance to TMP-SMZ[2] (P < 0.01) and an apparent increase in resistance to other antibiotics.

Conclusion: The excellent in vitro activity of linezolid and its reported in vivo effectiveness renders it an important therapeutic alternative to vancomycin in the treatment of MRSA infection.

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[1] MRSA = methicillin-resistant Staphylococcus aureus

[2] TMP-SMX = trimethoprim/sulfamethoxazole

Background: Heterotopic ossification is a common complication of hip surgery and musculoskeletal or brain traumas.

Objectives: To confirm by in vivo study that colchicine inhibits osteoblast cell proliferation with marked decrease in tissue mineralization.

Methods: Heterotopic ossification was induced in three groups of New Zealand white rabbits (females, 6 months old, weight 3–3.5 kg) by injecting 2 ml bone marrow drawn from the iliac crest into their right thigh muscle. To prevent heterotopic ossification, colchicine (0.25 mg/day) was administered orally for 4 weeks to two groups of adult rabbits: group A (preload group) – 1 week preceding bone marrow injection; group B – on day of injection; and group C – control group.

Results: After 4 weeks the rabbits were evaluated by radiographs and ultrasound for evidence of heterotopic ossification. At the end of the study histologic samples were taken from all the thighs. Imaging and histologic studies showed, with statistical significance, almost complete prevention of heterotopic ossification formation in group A (preload) and a marked decrease in group B, when compared with the controls in whom large new bone had formed at the injection site. These results indicated the inhibitory effects of colchicine on a bone-forming process in soft tissue such as heterotopic ossification.

Conclusions: The role of colchicine in preventing heterotopic ossification in other bone-forming conditions, such as hip arthroplasty or pelvic trauma, and after brain trauma, remains to be evaluated in a clinical setting.

Background: Gallium scintigraphy is frequently used in the evaluation of fever of unknown origin, although its utility has been addressed in only a few studies.

Objectives: To evaluate the utility of gallium scintigraphy in the evaluation of patients with FUO[1] in our department.

Methods: We reviewed the charts of all patients from our department who had undergone gallium scintigraphy during the years 1995–2002 for the evaluation of FUO and who met the criteria for the definition of FUO. Demographic, clinical and laboratory data in addition to the results of gallium scintigraphy were documented. The patients were divided into two groups: those with a normal gallium study (group 1) and those with an abnormal gallium study (group 2). The second group was further divided into two groups: those whose gallium study results contributed to the diagnosis of the cause of FUO (group 2A) and those whose gallium study results did not (group 2B).

Results: A total of 102 patients met the study criteria. The male: female ratio was 54:48 and the mean age ± SD was 62.4 ± 20 years. A final diagnosis had been reached in 63 patients (62%), among whom the etiology was infectious in 54%, neoplastic in 19% and immunologic/rheumatic in 16%. Forty-one patients (40% of all the patients) (Group 2) had an abnormal gallium scintigraphy, and in only 21 patients (21% of all the patients) (Group 2A) did the gallium study results contribute to the diagnosis of the cause of FUO. However, in only two patients from Group 2A (2% of all the patients in our study) was the contribution of gallium study considered significant or crucial to the diagnosis of the cause of FUO.

Conclusions: The utility of gallium scintigraphy in the evaluation of FUO is very limited.

Classic anticoagulant drugs, such as heparin and warfarin, are very effective. Although in use for more than 50 years, they have some clinical drawbacks. Heparin, now better termed unfractionated heparin, can only be used intravenously and its laboratory control is complicated. Warfarin is orally administered, but its therapeutic window is very narrow and patients need repeated laboratory tests. Moreover, both drugs are non-specific, as they inhibit the coagulation cascade at several steps. Pharmaceutic research has developed new drugs, some of which are already on the market, such as fondaparinux, a pentasaccharide that can interact with antithrombin, thus inhibiting factor Xa. This pentasaccharide is part of the parent heparin molecule and can be chemically synthesized, with the advantage of avoiding extractive compounds. Fondaparinux has a half-life compatible with once-a-day administration; modification of its structure (idraparinux) has led to more stable binding with antithrombin and to an increase in its half-life to allow once-a-week administration. Alternatives to oral anticoagulants have been developed following the study of some compounds like hirudin, which directly binds thrombin and blocks its catalytic site. One of these molecules, ximelagatran, is in advanced clinical development. Ximelagatran is converted into its active form, melagatran, in the circulation, and thrombin activity can be blocked by oral administration twice daily. There is no need for laboratory control and phase II and phase III studies are encouraging. The next few years should bring great changes in the treatment of patients with thromboembolic disorders.