Israel Medical Association Journal

The lethal poisoning of Alexander Litvinenco with the radioactive element polonium-210, and the risk that many civilians (including Israeli citizens) who were in the same location in London at the same time were exposed to radiation, was an unprecedented event in the western world. This was only the second known death due to ²¹⁰Po[1], a natural alpha radiation-emitting element. A task team was created to handle the event. The team comprised representatives from the Ministry of Health's advisory committee for radiological events (which includes the Israel Defense Force, the Israeli Atomic Energy Commission and the Ministry of Environmental Protection), the Public Health Services Central District, and a public relations expert. Forty-seven people were located and underwent an epidemiological inquiry, and urine samples for detection of ²¹⁰Po were sent abroad to a specialized laboratory. The radiotoxicological results were analyzed and evaluated by the expert team and follow-up recommendations were made. This unfamiliar and potentially stressful scenario was handled successfully by a multi-organizational multidisciplinary task team. The joint work of the task team was a real-life "exercise" simulating a radiological event in Israel. This team has recommended further evaluation of various vital missions in the event of any possible future radiological event, with special emphasis on a proactive communication approach to the media and the public.

Background: Syncope is a common clinical problem that often remains undiagnosed despite extensive and expensive diagnostic evaluation.

Objectives: To assess the diagnostic evaluation, costs and prognosis of patients hospitalized for syncope in a tertiary referral center according to discharge diagnosis.

Methods: We retrospectively reviewed the medical records of patients with a diagnosis of syncope discharged from a tertiary referral center in 1999. In addition, mortality data were obtained retrospectively a year after discharge for each patient.

Results: The study group comprised 376 patients. Discharge etiologies were as follows: vasovagal 26.6%, cardiac 17.3%, neurological 4.3%, metabolic 0.5%, unexplained 47.3%, and other 4%. A total of 345 patients were admitted to the internal medicine department, 28 to the intensive cardiac care unit, and 3 to the neurology department. Cardiac and neurological tests were performed more often than other tests, with a higher yield in patients with cardiac and neurological etiologies respectively. The mean evaluation cost was 11,210 ± 8133 shekels, and was higher in the ICCU[1] than in internal medicine wards (19,210 ± 11,855 vs. 10,443 ± 7314 shekels, respectively; P = 0.0015). Mean in-hospital stay was 4.9 ± 4.2 days, which was longer in the ICCU than in medicine wards (7.2 ± 5.6 vs. 4.6 ± 3.5 days, respectively; P = 0.024). Short-term mortality rates (30 days after discharge) and long-term mortality rates (1 year after discharge) were 1.9% and 8.8% respectively, and differed according to discharge etiology. LTM[2] rates were significantly higher in patients discharged with cardiac, neurological and unknown etiologies (not for vasovagal), compared with the general population of Israel (1 year mortality rate for the age-adjusted [65 years] general population = 2.2%). The LTM rate was higher in patients discharged with a cardiac etiology than in those with a non-cardiac etiology (15.4% vs. 7.4%, P = 0.04). Higher short and long-term mortality rates were associated with higher evaluation costs.

Conclusions: Hospitalization in a tertiary referral center for syncope is associated with increased mortality for most etiologies (except vasovagal), cardiac more than non-cardiac. Despite high costs of inpatient evaluation, associated with more diagnostic tests, longer in-hospital stay and higher mortality rates, nearly half of the patients were discharged undiagnosed. Outpatient evaluation should be considered when medically possible.

Background: The cognitive impairment (frontal, parietal) in many patients with multiple sclerosis does not correlate with the degree of neurological disability and disease duration. Frontal/prefrontal cognitive impairment requires neuropsychological diagnostic tools.

Objectives: To evaluate the clinical effect of IFNβ-1b[1] (Betaferon®) treatment on cognitive function and event-related potential as compared to the clinical course (EDSS[2]) in MS patients during 1 year of follow-up.

Methods: This prospective open-label design study included 16 consecutive patients with relapsing forms of MS attending the MS outpatient clinic. Mean EDSS score was calculated prior to starting treatment. Parietal lobe event-related potential P300 was elicited using an auditory physical stimulus to an alert subject. Mean P300 amplitude and latency were calculated for the group before treatment. The Wisconsin Card Sorting Test, which measures frontal lobe functions, was performed before the treatment. After 1 year of treatment a second P300 and Wisconsin Card Sorting Test were performed and the mean change between visit 1 and baseline was calculated for each parameter. Correlation between the change in P300 and the Wisconsin Card Sorting Test score at baseline was measured using the paired t-test.

Results: There was a significant reduction in P300 amplitude and latency after 1 year of treatment with IFNβ-1b: from 20.3 ± 8.3 μv to 13.1 ± 10.6 μv (P = 0.026) for amplitude, and from 312.9 ± 15.6 msec to 302.0 ± 17.0 msec (P = 0.002) for latency. The Perseverative Response (raw score) and the Perseverative Response U.S. Census age-matched standard score showed a significant improvement – from 20.7 ± 30.7 to 13.1 ± 10.6 (P = 0.001) and 96.7 ± 15.7 to 100.1 ± 11.1 (P = 0.0025) respectively – after 1 year of treatment. A mild but not significant improvement was observed on the EDSS after 1 year of treatment: 2.9 ± 0.5 to 2.8 ± 1.1.

Conclusions: A cognitive decline in MS patients may have a negative impact on the quality of life, affecting all active daily living domains. IFNβ-1b, a disease-modifying therapy, has demonstrated a positive therapeutic effect on cognitive dysfunction, unrelated to its effect on the EDSS score and course of the disease.

Background: Syndromic surveillance systems have been developed for early detection of bioterrorist attacks, but few validation studies exist for these systems and their efficacy has been questioned.

Objectives: To assess the capabilities of a syndromic surveillance system based on community clinics in conjunction with the WSARE[1] algorithm in identifying early signals of a localized unusual influenza outbreak.

Methods: This retrospective study used data on a documented influenza B outbreak in an elementary school in central Israel. The WSARE algorithm for anomalous pattern detection was applied to individual records of daily patient visits to clinics of one of the four health management organizations in the country.

Results: Two successive significant anomalies were detected in the HMO’s[2] data set that could signal the influenza outbreak. If data were available for analysis in real time, the first anomaly could be detected on day 3 of the outbreak, 1 day after the school principal reported the outbreak to the public health authorities.

Conclusions: Early detection is difficult in this type of fast-developing institutionalized outbreak. However, the information derived from WSARE could help define the outbreak in terms of time, place and the population at risk.

Objectives: To estimate the influence of phlebotomies on large artery (C1) and small artery compliance (C2) in PV patients by using non-invasive methods.

Methods: Short-term hemodynamic effects of phlebotomy were studied by pulse wave analysis using the HDI-Pulse Wave CR2000 (Minneapolis, MN, USA) before and immediately after venesection (300–500 ml of blood). We repeated the evaluation after 1 month to measure the long-term effects.

Results: Seventeen PV patients were included in the study and 47 measurements of arterial compliance were performed: 37 for short-term effects and 10 for long-term effects. The mean large artery compliance (C1) before phlebotomy was 12.0 ml/mmHg x 10 (range 4.5–28.6), and 12.6 ml/mmHg x 10 (range 5.2–20.1) immediately after phlebotomy (NS). The mean small artery compliance (C2) before and immediately after phlebotomy were 4.4 mg/mmHg x 10 (range 1.2–14.3) and 5.5 mg/mmHg x 10 (range 1.2–15.6) respectively (delta C2–1.1, P < 0.001). No difference in these parameters could be demonstrated in the long-term arm.

Conclusions: Phlebotomy immediately improves arterial compliance in small vessels of PV patients, but this effect is short lived.

Objectives: To investigate and compare the epidemiologic, clinical and laboratory characteristics of cancer and non-cancer patients hospitalized with venous thromboembolism in a large referral medical center in Israel.

Methods: Between February 2002 and February 2003, patients diagnosed at the Rambam Medical Center as suffering from VTE[1] (deep vein thrombosis and/or pulmonary embolism), based on diagnostic findings on Doppler ultrasonography, spiral computed tomography scan or lung scan showing high probability for pulmonary embolism, were prospectively identified and evaluated. In addition, at the conclusion of the study period, the reports of spiral chest CT scans, performed during the aforementioned period in this hospital, were retrospectively reviewed to minimize the number of unidentified cases. Blood samples were drawn for evaluation of the coagulation profile.

Results: Altogether, 147 patients were identified and 153 VTE events diagnosed, accounting for 0.25% of all hospitalizations during the study period. The cancer group included 63 patients (43%), most of whom had advanced disease (63%). The most common malignancies were cancer of the lung (16%), breast (14%), colon (11%) and pancreas (10%). Of 121 venous thromboembolic events (with or without pulmonary embolism) there were 14 upper extremity thromboses (12%). The most common risk factors for VTE, except malignancy, were immobilization (33%), surgery/trauma (20%) and congestive heart failure (17%). There was no difference in prevalence of various risk factors between cancer and non-cancer patients. During an acute VTE event, D-dimer levels were higher in cancer patients than non-cancer patients (4.04 ± 4.27 vs. 2.58 ± 1.83 mg/L respectively, P = 0.0550). Relatively low values of activated protein C sensitivity ratio and normalized protein C activation time were observed in both cancer and non-cancer groups (2.05 ± 0.23 vs. 2.01 ± 0.33 and 0.75 ± 0.17vs. 0.71 ± 0.22, respectively). These values did not differ significantly between the groups.

Conclusion: The proportion of cancer patients among patients suffering from VTE was high. Their demographic, clinical and laboratory characteristics (during an acute event) were not different from those of non-cancer patients, except for higher D-dimer levels.

Background: Men and postmenopausal women with iron deficiency anemia are routinely evaluated to exclude a gastrointestinal source of suspected internal bleeding. Iron deficiency anemia in premenopausal women is often treated with simple iron replacement, under the assumption that the condition is due to excessive menstrual blood loss.

Objectives: To determine the yield of endoscopy evaluations in premenopausal women with iron deficiency anemia.

Methods: Upper and lower gastrointestinal endoscopic examinations were conducted in 45 premenopausal women with iron deficiency anemia not related to gynecologic or nutritional causes.

Results: Forty-three of the 45 women fulfilled the entry criteria and were enrolled. Their mean age was 35 ± 15 years and their mean hemoglobin level 9.3 ± 2.3 g/dl. Twenty‑eight upper gastrointestinal lesions were demonstrated in 24 of the 43 patients (55.8%): erosive gastritis in 12 (27.9%), erosive duodenitis in 4 (9.3%), erosive esophagitis in 3 (7.0%), hiatus hernia (with Cameron lesions) in 3 (7.0%), active duodenal ulcer in 1 (2.3%) and hyperplastic polyp (10 mm) in 1 (2.3%). Five lower gastrointestinal lesions were detected in 5 patients (16.3%): 2 (4.6%) had adenocarcinoma of the right colon, 2 (4.6%) had pedunculate adenomatous polyp > 10 mm, and 1 (2.3%) had segmental colitis (Crohn's disease). One patient (2.3%) had pathologic findings in both the upper and lower gastrointestinal tracts.

Conclusions: Our findings of a gastrointestinal source of chronic blood loss in 28 of 43 premenopausal women with iron deficiency anemia (65.1%) suggest that this population will benefit from bi‑directional endoscopic evaluations of the gastrointestinal tract.

Objectives: To determine the effectiveness of a neuroreflexology-based screening test, specifically the Medex device (Medex Screen Ltd.), for diagnosing patients undergoing conventional internal organ assessment, in a hospital setting.

Methods: Patients admitted to an internal medicine department, who met the inclusion criteria and agreed to participate, underwent conventional medical evaluation that included past medical history and physical examination. Another examination was conducted by a second physician using the Medex device to determine internal organ pathologies. A third researcher compared the actual “conventional” diagnosis with the Medex device output using standard statistical analysis.   

Results: Overall, 150 patients participated in the study. Correlation was significant for all categories (P < 0.01) except for blood and lymphatic disease. A high sensitivity (>70%) was measured for cardiovascular, respiratory, gastrointestinal and genitourinary diseases. The highest measure of agreement, as represented by the Cohen-Kappa factor, was found for respiratory disease (0.57).

Conclusions: Although the exact mechanism is not entirely clear, measurement of electroskin impedance of dermal-visceral zones has the potential to serve as a screening tool for inner organ pathologies. Further research should be conducted to create more evidence to support or dispute the use of this technique as a reliable diagnostic tool.

Objectives: To investigate the spectrum of findings in 32 consecutive patients with chest pain who underwent CT coronary angiogram in order to determine the clinical situations that will benefit most from this new technique.

Methods: Thirty-two patients with chest pain were studied by MDCT[1] using 4 x 1 mm cross-sections, at 500 msec rotation with pitch 1–1.5, intravenous non-ionic contrast agent and a retrospectively ECG-gated reconstruction algorithm. The heart anatomy was evaluated using multi-planar reconstructions in the axial, long and short heart axes planes. Coronary arteries were evaluated using dedicated coronary software and the results were compared to those of the conventional coronary angiograms in 12 patients. The patients were divided into four groups according to the indication for the study: group A – patients with high probability for coronary disease; group B – patients after CCA[2] with undetermined diagnosis; group C – patients after cardiac surgery with possible anatomic derangement; and group D – symptomatic patients after coronary artery bypass graft, before considering conventional coronary angiography.

Results: Artifacts caused by coronary motion, heavy calcification and a lumen diameter smaller than 2 mm were the most frequent reasons for non-evaluable arteries. Assessment was satisfactory in 83% of all coronary segments. The overall sensitivity of 50% stenosis was 74% (85% for main vessels) with a specificity of 96%. Overall, the CTCA[3] results were critical for management in 18 patients.

Conclusions: Our preliminary experience suggests that CTCA is a reliable and promising technique for the detection of coronary artery stenosis as well as for a variety of additional cardiac and coronary structural abnormalities.

Objectives: To evaluate the sensitivity, specificity, accuracy, and positive and negative predictive values of FNAB[1] in cases of a solitary thyroid nodule.

Methods: The preoperative FNAB results of 170 patients who underwent thyroidectomy due to a solitary thyroid nodule were compared retrospectively with the final postoperative pathologic diagnoses.

Results: In cases of a solitary thyroid nodule, FNAB had a sensitivity of 79%, specificity of 98.5%, accuracy of 87%, and positive and negative predictive values of 98.75% and 76.6% respectively. All cases of papillary carcinoma diagnosed by FNAB proved to be malignant on final histology, while 8 of 27 cases of follicular adenoma detected by preoperative FNAB were shown to be malignant on final evaluation of the surgical specimen.

Conclusions: FNAB cytology reduces the incidence of thyroidectomy since this method has excellent specificity and sensitivity and a low rate of false-negative results. It proved to be cost-effective and is recommended as the first tool in the diagnostic workup in patients with thyroid nodules.

Objectives: To characterize the academic background of graduates, evaluate their attitudes towards current and alternative medical education programs, and examine subgroups among graduates according to gender, medical school, high school education, etc.

Methods: The survey included graduates from all four Israeli medical schools who graduated between the years 1981 and 2000 in a sample of 1:3. A questionnaire and stamped return envelope were sent to every third graduate; the questionnaire included open and quantitative questions graded on a scale of 1 to 5. The data were processed for the entire graduate population and further analyzed according to subgroups such as medical schools, gender, high school education, etc.

Results: The response rate was 41.3%. The survey provided a demographic profile of graduates over a 20 year period, their previous educational and academic background, additional academic degrees achieved, satisfaction, and suggestions for future medical education programs.

Conclusions: The profile of the medical graduates in Israel is mostly homogenous in terms of demographics, with small differences among the four medical schools. In line with recommendations of the graduates, and as an expression of the changing requirements in the healthcare system and the medical profession, the medical schools should consider alternative medical education programs such as a bachelor’s degree in life sciences followed by MD studies, or education programs that combine medicine with disciplines such as law, engineering, computer science, etc.

Objective: To present our algorithm of urgent and elective donor selection.

Methods: Urgent selection is expeditious and protocol‑based. Elective selection permits a comprehensive process. Both include medical, psychosocial and surgical-anatomic evaluations. Liver volumes and vascular anatomy are evaluated with computerized tomographic angiography. Informed consent is obtained after painstaking explanations. Independent institutional committees review and approve all cases.

Results: Between July 2003 and June 2004 we evaluated 43 potential live donors for 12 potential recipients (fulminant hepatic failure, n=5; chronic end-stage liver disease, n=6); primary graft non-function, n=1). Thirty-three candidates (76%) were excluded due to blood type incompatibility (n=14, 42%), incompatible anatomy (n=8, 24%) – including problematic volume distribution (n=2) or vascular anatomy (n=6) – psychosocial issues (n=4, 12%), or medical co-morbidity (n=7, 22%). Five recipients (FHF[1], n=4; chronic ESLD[2], n=1) were successfully transplanted from living donors. In the acute setting, two patients (FHF, PGNF[3]) died in the absence of an appropriate donor (cadaveric or living donor). In the elective group, one patient died of unexpected variceal bleeding and one received a cadaveric graft just before the planned living donor transplantation was performed. One candidate was transplanted overseas and two cases are scheduled. The ratio of compatibility for donation was 34% (10/29) for blood type-compatible candidates.

Conclusions: Donor selection for living donor liver transplantation is a complex, labor-intensive multidisciplinary process. Most exclusions are due to blood type incompatibility or anatomic details. Psychosocial aspects of these donations warrant special attention.

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[1] FHF = fulminant hepatic failure

[2] ESLD = chronic end-stage liver disease

[3] PGNF = primary graft non-function