Israel Medical Association Journal

Background: The term chronic multi-symptom illness refers to a spectrum of pain disorders, such as fibromyalgia and chronic fatigue syndrome, that are characterized by unexplained chronic pain, fatigue, and cognitive and mood complaints

Objectives: To examine the hypothesis that exercise cessation is associated with symptoms similar to CMI[1] in well-trained amateur athletes.

Methods: The study, conducted in running and triathlon clubs in Israel, involved 26 asymptomatic healthy athletes who regularly exercise 6.75 ± 3.65 hours a week. All athletes were instructed to refrain from physical activity for 7 days. All underwent a complete physical exam, rheumatological assessment including non-articular tenderness threshold (using dolorimeter) and tender points. In addition they completed the SF-36 quality of life questionnaire. Assessments were conducted before exercise cessation and 7 days later.

Results: Seven days after sports deprivation all subjects were significantly more tender by all tender measures (P < 0.001) (dolorimeter thresholds and tender point count). There was also a significant reduction in the scores for physical role function (P < 0.001), emotional role function (P < 0.001) and summary subscales of the SF-36 questionnaire after exercise cessation.

Conclusions: Exercise deprivation is associated with change in non-articular tenderness threshold and reduction in quality of life scores. This may be associated with the development of chronic multi-symptom illness.

Background: The rate of brain abnormalities in asymptomatic term neonates varies substantially in previous studies. Some of these rates may justify general screening of healthy newborns by head ultrasound.

Objectives: To assess the incidence of intracranial abnormalities among asymptomatic term newborns with HUS[1] and to detect high-risk populations that might need such screening.

Methods: This was a prospective study in 493 term newborns who underwent HUS and a neurological evaluation during the first 3 days of life. The neurological examination results were unknown to the sonographist and the examiner was blinded to the HUS findings. The abnormal HUS findings were classified as significant or non-significant according to the current literature.

Results: Abnormal HUS was found in 11.2% of the neonates. Significant findings were noted in 3.8% of the infants. There was no association between non-structural HUS findings (hemorrhage or echogenicity) and mode of delivery. There was no relationship between any HUS abnormality and birth weight, head circumference and maternal age, ethnicity, education or morbidity. The rate of abnormal neurological, hearing or vision evaluation in infants with a significant abnormal HUS (5.2%) was comparable to the rate in infants with normal or non-significant findings on HUS (3.1%).

Conclusions: There is no indication for routine HUS screening in apparently healthy term neonates due to the relatively low incidence of significant brain abnormalities in these infants in our population.

Background: Traditionally, medication dosage was based on clinical and demographic parameters, but drug metabolism was recently recognized as an important factor for proper dosing and prediction of side effects. Metabolic considerations are crucial when administering drugs with a narrow therapeutic index, such as those of the thioguanides family (azathioprine and 6-MP). These can cause life-threatening myelosuppression due to low activity of a critical metabolic enzyme, thiopurine S-methyl transferase. A number of single nucleotide substitutions encoding variant enzymes account for most enzyme deficiencies.

Objectives: To determine the frequency of individuals from different Israeli ethnic groups who may be at risk for drug toxicity from drugs of the thioguanide family due to enzymatic variants.

Methods: DNA analysis was performed using polymerase chain reaction methods. We tested TPMT[1] allelic variants TPMT*3A (G460A, A719G), TPMT*3B (G460A) and TPMT*3C (A719G) in five subpopulations in Israel: mixed-origin Israeli Jews, Arabs, Druze, Jews of Kurdish extraction, and Ethiopian Jews.

Results: The Druze (P = 0.0002) and Ethiopian Jewish (P = 0.015) subpopulations had a significantly unique distribution of allelic variants compared to the rest of the Israeli population. The Druze subpopulation showed a high number of TPMT variants with decreased activity, and a homozygote for TPMT*3A/ *3A was detected.  Ethiopian Jews were found to carry mainly the TPMT*3C variant, also observed in other studies of African populations.

Conclusions: It is advisable that Druze patients be tested for the TPMT enzyme before starting treatment with 6-MP or azathioprine. Such testing may also be considered for other Israeli ethnic subgroups.

Background: Gastric cancer continues to be a leading cause of cancer death. The treatment approach varies, and preoperative staging is therefore crucial since an exploratory laparotomy for unresectable gastric cancer will be followed by an unacceptably high morbidity and mortality rate.

Objectives: To assess the added value of diagnostic laparoscopy to conventional methods of diagnosis such as computed tomography in avoiding unnecessary laparotomies.

Methods: A retrospective study on 78 patients scheduled for curative gastrectomy based on CT staging was conducted. DL[1] was performed prior to exploratory laparotomy.

Results: In 23 of 78 patients (29.5%), unexpected peritoneal spread not detected on preoperative CT was found. Fifty-five patients underwent radical gastrectomy, 15 patients were referred for downstaging and 8 patients underwent a palliative procedure.

Conclusions: Based on our results, DL should be considered in all gastric cancer patients scheduled for curative gastrectomy.

Background: During the last few decades much effort has been invested into lowering smoking rates due to its heavy burden on the population's health and on costs for the health care services.

Objectives: To compare trends in smoking rates between adult Arab men and Jewish men and women during 2000–2008.

Methods: Six random telephone surveys were conducted by the Israel Center for Disease Control in 2000–2008 to investigate smoking rates. The number of respondents was 24,976 Jews men and women and 2564 Arab men. The percent of respondents reporting being current smokers was calculated for each population group (Jews and Arabs) by age, gender and education, and were studied in relation to time.

Results: Among Jewish men aged 21–64 smoking declined during 2000–2008 by about 3.5%. In the 21–44 age group this decline occurred only among respondents with an academic education. Among Jewish women this decline also occurred at ages 21–64, and in the 45–64 age group this decline was due only to a decline in smoking among those with an academic education. Among Arab men aged 21–64 an increase in smoking rates of about 6.5% was observed among both educated and less educated respondents.

Conclusions: Smoking prevalence is declining in Israel among Jews, but not among Arab men. The larger decrease in smoking rates among academics will, in the future, add to the inequalities in health between the lower and higher socioeconomic status groups and between Arabs and Jews. This calls for tailored interventions among the less educated Jews and all Arab men.

Background: Appropriate antibiotic use is of both clinical and economic significance to any health system and should be given adequate attention. Prior to this study, no in-depth information was available on antibiotic use patterns in the emergency department of Hadassah Medical Center.

Objectives: To describe the use and misuse of antibiotics and their associated costs in the emergency department of Hadassah Medical Center.

Methods: We analyzed the charts of 657 discharged patients and 45 admitted patients who received antibiotics in Hadassah Medical Center’s emergency department during a 6 week period (29 April – 11 June 2007). A prescription was considered appropriate or inappropriate if the choice of antibiotic, dose and duration by the prescribing physician after diagnosis was considered suitable or wrong by the infectious diseases consultant evaluating the prescriptions according to Kunin’s criteria.

Results: The overall prescribing rate of antibiotics was 14.5% (702/4830) of which 42% were broad- spectrum antibiotics. The evaluated antibiotic prescriptions numbered 1105 (96 prescriptions containing 2 antibiotics, 2 prescriptions containing 3 antibiotics), and 54% of them were considered appropriate. The total inappropriate cost was 3583 NIS[1] (1109 USD PPP[2]) out of the total antibiotic costs of 27,300 NIS (8452 USD PPP). The annual total antibiotic cost was 237,510 NIS (73,532 USD PPP) and the annual total inappropriate cost was 31,172 NIS (9648 USD PPP). The mean costs of inappropriate prescriptions were highest for respiratory (112 NIS, 35 USD PPP) and urinary tract infection (93 NIS, 29 USD PPP). There were more cases when the optimal cost was lower than the actual cost (N=171) than when optimal cost was higher than the actual cost (N=9). In the first case, the total inappropriate costs were 3805 NIS (1,178 USD PPP), and in the second case, -222 NIS (68.7 USD PPP).

Conclusions: The use of antibiotics in emergency departments should be monitored, especially in severely ill patients who require broad-spectrum antibiotics and for antibiotics otherwise restricted in the hospital wards. Our findings indicate that 12% of the total antibiotic costs could have been avoided if all prescriptions were optimal.

Background: Although the presence of bacteria in the cervix is not a sign of disease, the majority of pathogens involved in pelvic inflammatory disease originate from this "normal" flora.

Objectives: To assess the distribution of cervical non-gonococcal and non-chlamydial bacteria in hospitalized women with PID[1] and the bacteria's antibiotic sensitivity.

Methods: We retrospectively evaluated the cultures obtained from the uterine cervix over a 1 year period (2008) at Wolfson Medical Center, Holon. The distribution of cervical non-gonococcal and non-chlamydial bacteria in women with PID and the bacteria's antibiotic sensitivity was compared to that in our previous 1 year study that was performed at Kaplan Medical Center, Rehovot (1988–89). 

Results: In 2008, a total of 412 cultures were obtained of which 126 (30.5%) were sterile. The prevalence of negative cultures was similar in 2008 and in 1988, namely, 30.5% and 33.7%, respectively (P = 0.23). PID was finally diagnosed in 116 patients with positive cultures. The most prevalent bacteria in the 2008 study were Enterococcus species and Escherichia coli – 24.0 % and 26.4% respectively compared to 18.0% and 38.1% in the 1988 study, with the decrease in E. coli isolates being significant (P = 0.0003). In 2008 the antimicrobial sensitivity for various antibiotics ranged from 44.3% to 100.0% (median 90.2%) while in 1988 it ranged from 2.9% to 80.1% (median 51.9%).

Conclusions: The cervical bacterial flora in hospitalized women with PID did not vary significantly between 1988 and 2008. However, antimicrobial sensitivity of the isolated bacteria increased dramatically, probably due to a decrease in resistance to antibiotics.

Background: Hypovitaminosis D has been shown to be extremely common in various regions around the world, mostly at high latitudes. Israel is characterized by certain features – cultural (e.g., ethnic isolates) and geographic (e.g., sunny climate) – that have been identified for their possible association with vitamin D status.

Objectives: To conduct an ecological study on a representative sample of the population of Israel, testing vitamin D status across age groups, genders, ethnic groups, and seasons.

Methods: We obtained serum samples from 195 healthy Israeli volunteers representing a broad demographic spectrum. Serum concentrations of 25(OH)D were measured with the commercial kit Liaison 25(OH)D Assay (DiaSorin, Italy).

Results: The mean vitamin D level for the entire cohort was surprisingly low (22.9 ± 10.1 ng/ml), with 149 subjects (78%) suffering from vitamin D insufficiency (< 30 ng/ml). Vitamin D status was better in infants than in older age groups. Differences by gender were significant only in the infant age group (i.e., vitamin D status was worse among females) and were not prominent across older ages. Israelis of Ashkenazi origin had higher vitamin D mean levels than those of Sephardic origin, who, in turn, had higher vitamin D levels than Arab subjects (31.4 ± 12, 24.1 ± 10, and 17.6 ± 9 ng/ml respectively). With regard to season, there were no differences between the samples collected in winter and the samples collected in summer.

Conclusions: The results suggest that hypovitaminosis D is common across all ages, genders and seasons in Israel, a country characterized by a sunny Mediterranean climate. Specific ethnic groups may be at especially high risk.

Background: The incidence of cutaneous leishmaniasis in northern Israel began to rise in 2000, peaking at 41.0 per 100,000 in the Kinneret subdistrict during the first half of 2003.

Objectives: To examine the morbidity rates of CL[1] in northern Israel during the period 1999–2003, which would indicate whether new endemic areas were emerging in this district, and to identify suspicious hosts.

Methods: The demographic and epidemiologic data for the reported cases (n=93) were analyzed using the GIS and SPSS software, including mapping habitats of suspicious hosts and localizing sites of infected sand flies.

Results: The maximal incidence rate in the district was found in the city Tiberias in 2003: 62.5/100,000 compared to 0–1.5/100,000 in other towns. The cases in Tiberias were centered on the peripheral line of two neighborhoods, close to the habitats of the rock hyraxes. Sand flies infected with Leishmania tropica were captured around the residence of those affected. Results of polymerase chain reaction were positive for Leishmania tropica in 14 of 15 tested patients.

Conclusions: A new endemic CL area has emerged in Tiberias. The most suspicious reservoir of the disease is the rock hyrax.

Background: Coronary CT angiography is an accurate imaging modality; however, its main drawback is the radiation dose. A new technology, the "step and shoot," which reduces the radiation up to one-eighth, is now available.

Objectives: To assess our initial experience using the "step-and-shoot" technology for various vascular pathologies.

Methods: During a 10 month period 125 consecutive asymptomatic patients (111 men and 14 women aged 25–82, average age 54.9 years) with various clinical indications that were appropriate for step-and-shoot CCTA[1] (regular heart rate < 65 beats/minute and body weight < 115 kg) were scanned with a 64-slice multidetector computed tomography Brilliance scanner (Philips, USA). The preparation protocol for the scan was the same as for the regular coronary CTA. All examinations were interpreted by at least one experienced radiologist and one experienced interventional cardiologist. The quality of the examinations was graded from 1 (excellent imaging quality of all coronary segments) to 4 (poor quality, not diagnostic). There were 99 patients without a history of coronary intervention, 13 after coronary stent deployment (19 stents), and 3 after coronary artery bypass graft.

Results: Coronary interpretation was obtained in 122 examinations (97.6%). The imaging quality obtained was as follows: 103 patients scored 1 (82.4%), 15 scored 2 (12%), 4 scored 3 (3.2%) and 3 scored 4 (2.4%). The grades were unrelated to cardiac history or type of previous examinations. Poor image quality occurred because of sudden heart rate acceleration during the scan (one patient), movement and respiration (one patient), and arrhythmia and bad scan timing (in one). Two patients were referred to percutaneous coronary intervention based on the CCTA findings, which correlated perfectly.

Conclusions: Step-and-shoot CCTA is a reliable technique and CCTA algorithm comparable to the regular CCTA. This technique requires the lowest radiation dose, as compared to other coronary imaging modalities, that can be used for all CCTA indications based on the inclusion criteria of low (> 65 bpm) and stable heart rate.

Background: For patients with ventricular tachyarrhythmias, implantable cardioverter defibrillators are a mainstay of therapy to prevent sudden death. However, ICD[1] shocks are painful, can result in clinical depression, and do not offer complete protection against death from arrhythmia. Radiofrequency catheter ablation of ventricular tachycardia in the setting of ischemic cardiomyopathy has emerged recently as a useful adjunctive therapy to ICD.

Objectives: To assess the feasibility, safety and efficacy of our initial experience in ablation of scar-related VT[2].

Methods: Eleven patients (all males, mean age 71 ± 8 years) with drug-refractory ischemic VT were referred to our center for scar mapping and ablation procedures using the CARTO navigation system.

Results: Eleven clinical VTs (mean cycle length 436 ± 93 ms) were induced in all patients. An endocardial circuit, identified by activation, entrainment and/or pace mapping, was found in eight patients with stable VT. These patients were mapped and ablated during VT. Three patients had predominantly unstable VT and linear ablation lesions were performed during sinus rhythm. Acute success, defined as termination of VT and or non-inducibility during programmed electrical stimulation, was found in 9 patients (82%). During follow-up, a significant reduction in tachyarrythmia burden was observed in all patients who had successful initial ablation, except for one who had recurrence of VT 2 days after the procedure and died 2 weeks later.

Conclusions: Ablation of ischemic VT using electroanatomic scar mapping is feasible, has an acceptable success rate and should be offered for ischemic patients with recurrent uncontrolled VT.

Background: Multiple case series, mostly highly selected, have demonstrated a very high mortality following acute basilar artery occlusion. The more widespread availability and use of non-invasive vascular imaging over recent years has increased the rate of ABAO[1] diagnosis.

Objectives: To estimate the proportion of diagnosed ABAO among all-cause ischemic stroke in an era of increasing use of non-invasive vascular imaging and to compare the characteristics and outcomes between these two groups.

Methods: We compared 27 consecutive cases of ABAO identified in a university hospital between 2003 and 2007 to 311 unselected cases of ischemic stroke from two 4 month surveys.

Results: ABAO diagnosis increased from 0.3% of all-cause ischemic stroke (2003–2004) to 1.1% (2007), reflecting the increased use of non-invasive vascular imaging. In comparison to all-cause ischemic stroke, ABAO patients were younger (mean age 60 vs. 71 years), were more likely to be male (89% vs. 60%), had less atrial fibrillation (7% vs. 26%), more severe strokes (baseline NIHSS over 20: 52% vs. 12%), higher admission white cell count (12,000 vs. 9000 cells/mm³) lower admission systolic blood pressure (140 ± 24 vs. 153 ± 27 mmHg), higher in-hospital mortality rates (30% vs. 8%) and worse functional outcome (modified Rankin scale ≤ 3, 22% vs. 56%) (P < 0.05 for all). Rates of reperfusion therapy for ABAO increased from 0 in 2003–2004 to 60% in 2007.

Conclusions: In this study, ABAO patients represented approximately 1% of all-cause ischemic stroke and were about a decade younger than patients with all-cause ischemic stroke. We report a lower ABAO mortality compared to previous more selected case series; however, most survivors had a poor functional outcome. Given the marked clinical heterogeneity of ABAO, a low threshold for non-invasive vascular imaging with a view to definitive reperfusion treatment is needed.