Israel Medical Association Journal

Background: Rapid reperfusion of an infarct-related artery is crucial for the successful treatment of ST elevation myocardial infarction. Every effort should be made to shorten door-to-balloon time.

Objectives: To investigate whether bypassing the emergency room (ER) has a positive influence on door-to-balloon time in patients presenting with ST elevation myocardial infarction (STEMI) and whether the reduction in door-to-balloon time improves patients’ clinical outcome.

Methods: We analyzed data of 776 patients with STEMI[1] from the 2004 and the 2006 Acute Coronary Syndrome Israeli Survey (ACSIS) registry. The ACSIS[2] is a biennial survey on acute myocardial infarction performed in all 25 intensive cardiac care units in Israel during a 2-month period. Twenty-five percent of patients (193 of 776) arrived directly to the intensive cardiac care unit (ICCU) and 75% (583 of 776) were assessed first in the ER[3]. We compared door-to-balloon time, ejection fraction, 30 days MACE (major adverse cardiac and cerebrovascular events) and 30 days mortality in the two study groups.

Results: There was significantly shorter door-to-balloon time in the direct ICCU group as compared with the ER group (45 vs. 79 minutes, P < 0.002). Patients in the direct ICCU group were more likely to have door-to-balloon time of less than 90 minutes in accordance with ACC/AHA guidelines (88.7% vs. 59.2%, P < 0.0001). Moreover, patients in the direct ICCU group were less likely to have left ventricular ejection fraction < 30% (5.4% vs. 12.2%, P = 0.045) and less likely to have symptoms of overt congestive heart failure. Lastly, 30 days MACE[4] was significantly lower in the direct ICCU group (22 vs. 30%, P < 0.004).

Conclusions: There is significant reduction of the door-to-balloon time in the direct ICCU admission strategy. This reduction translates into improvement in clinical outcome of patients. It is reasonable to apply the direct ICCU strategy to patients with STEMI.

Background: The age-standardized incidence rate of invasive cervical cancer in Israeli Jewish women is persistently low. Selected demographic characteristics of Israeli Jewish women with cervical squamous cell carcinoma (SCC) were reported recently. 

Objectives: To assess selected clinical characteristics of Israeli Jewish women with cervical SCC.

Methods: Included were all Israeli Jewish women with SCC diagnosed during the 3-year period 2002­–2004. Data were obtained from the Israel National Cancer Registry and the Central Population Registry. Discharge summaries of the patients were reviewed and clinical data were abstracted.

Results: The study was based on 350 Israeli Jewish women with histologically confirmed cervical SCC diagnosed during the 3-year study period. The median age of the patients was 50.3 years. The most common main complaint was discharge/bleeding (35.7%) and only a small percentage (7.4%) was diagnosed subsequent to an abnormal cytological smear. The rate of patients diagnosed in stage I was 47.7%. The overall absolute 5-year survival and survival in stage I was 70% and 83.8% respectively. The rate of Israeli born patients diagnosed in stage I and their overall absolute 5-year survival was significantly higher than in the other ethnic groups.

Conclusions: Age, the most frequent main complaint, the percent of patients diagnosed in stage I and the 5-year survival (overall and in stage I) are similar to data in other countries. The survival of Israeli born women seems to be better than that of other ethnic groups.
 

Background: Major advances in the treatment of perinatal asphyxial–hypoxic ischemic encephalopathy followed the translation of hypothermia animal studies into successful randomized controlled clinical trials that substantially influenced the current standard of care.

Objectives: To present our preliminary experience with the first cases of clinical application of therapeutic hypothermia for PA-HIE[1] in what we believe is the first report on non-experimental hypothermia for PA-HIE from Israel.

Methods: We reviewed the medical records, imaging scans, electroencephalograms and outcome data of the six identified asphyxiated newborns who were managed with hypothermia in our services in 2008–2009.

Results: All asphyxiated newborns required resuscitation and were encephalopathic. Systemic hypothermia (33.5ºC) was begun at a median age of 4.2 hours of life (range 2.5–6 hours) and continued for 3 days. All six infants showed a significantly depressed amplitude integrated electroencephalography background, and five had electrographic seizures. One infant died (16%) after 3.5 days. Major complications included fat necrosis and hypercalcemia (n=1), pneumothorax (n=1), and meconium aspiration syndrome (n=2). None of the infants developed major bleeding. Neurodevelopmental follow-up of the five surviving infants at median age 7.2 months (4.1–18.5 months) revealed developmental delays (Battelle screening), with their motor scores ranging from -1 to +1 standard deviation (Bayley scale). None developed feeding problems, oculomotor abnormalities, spasticity or seizures.

Conclusions: Our preliminary experience with this novel modality in a large Tel Aviv neonatal service is consistent with the clinical findings of published trials.

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: 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: 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.

Background: The prevalence of aortic stenosis increases with advancing age. Once symptoms occur the prognosis in patients with severe aortic stenosis is poor. The current and recommended treatment of choice for these patients is surgical aortic valve replacement. However, many patients, mainly the very elderly and those with major comorbidities, are considered to be at high surgical risk and are therefore denied treatment. Recently, a transcatheter alternative to surgical AVR[1] has emerged.

Objectives: To describe the first year experience and 30 day outcome of transcatheter aortic self-expandable CoreValve implantation in Israel.

Methods: Transcatheter aortic valve implantation using the CoreValve system has been performed in Israel since September 2008. In the following year 55 patients underwent CoreValve TAVI[2] in four Israeli centers.

Results: Patients' mean age was 81.7 ± 7.1 years; there were 35 females and 20 males. The mean valve area by echocardiogram was 0.63 ± 0.16 cm². The calculated mean logistic Euroscore was 19.3 ± 8%. Following TAVI, mean transvalvular gradient decreased from baseline levels of 51 ± 13 to 9 ± 3 mmHg. The rate of procedural success was 98%. One patient died on the first day post-procedure (1.8%) and all-cause 30 day mortality was 5.5% (3 of 55 patients). One patient had a significant post-procedural aortic regurgitation of > grade 2. Symptomatic improvement was evident in most patients, with reduction in functional capacity grade from 3.2 ± 0.6 at baseline to 1.4 ± 0.7. The most common post-procedural complication was complete heart block, which necessitated permanent pacemaker implantation in 37% of patients.

Conclusions: The Israeli first year experience of transcatheter aortic valve implantation using the CoreValve self-expandable system demonstrates an effective and safe procedure for the treatment of severe aortic stenosis in patients at high surgical risk.

Background: In the last decade the diagnosis of celiac disease has increasingly been made in adults.

Objectives: To determine disease prevalence (including silent and potential disease) in this population group.

Methods: We performed serologic screening of celiac disease in a representative and homogenous sample of a young adult general population in Israel, namely, 18 year old military conscripts, in 2003. Serologic screening was performed on serum samples randomly obtained from 850 healthy recruits (male/female = 1.1). Immunoglobulin A anti-tissue transglutaminase was determined by enzyme-linked immunosorbent assay. In cases of IgA[1] deficiency, IgG anti-endomysial antibodies were determined. A small intestinal biopsy was offered to all patients with positive serology.

Results: The prevalence of overt CD[2] diagnosed prior to recruitment was 0.12% (0.1% in men and 0.14% in women). The overall prevalence based on positive serology was 1.1%. Six of nine subjects with positive serology agreed to undergo endoscopy and intestinal biopsies. In all cases, biopsies were compatible with celiac disease (five biopsies were graded as Marsh 3a and one as Marsh 3b). One subject previously reporting irritable bowel-like symptoms was diagnosed with overt atypical CD. The prevalence of overt CD diagnosed by screening was 0.12%. The ratio of overt to silent CD was 1:8. No cases of potential disease were encountered.

Conclusions: Our findings suggest that CD is highly prevalent in the young adult population in Israel. Serologic screening for CD is a reliable and simple method for diagnosing this disease before symptoms or complications develop. 

[1] Ig = immunoglobulin

[2] CD = celiac disease

Background: Human parvovirus B19 is a global and common infectious pathogen in humans, primarily in children.

Objectives: To assess the immunoglobulin G seroprevalence of B19 in children in Israel.

Methods: Overall, 128 previously healthy children (1.5–17 years old) hospitalized for various diseases other than acute human parvovirus B19 infection were assessed for IgG[1] to the virus by enzyme-linked immunosorbent assay. 

Results: The IgG seroprevalence increased from 22% in children aged 1.5–9 years to 52% in older children (P = 0.001).

Conclusions: Our data suggest that most acute parvovirus B19 infections in Israel occur in the early school years, and that by 18 years of age 50% of Israeli children have been infected by the virus.

[1] IgG = immunoglobulin G

Background: Severe hearing impairment can have devastating effects on social integration and vocational opportunities.

Objectives: To investigate how well – or poorly – individuals who underwent cochlear implantation as children integrated into the general Israeli hearing community.

Method: We sent a questionnaire to the 30 subjects ≥ 18 years old who underwent cochlear implants our department from 1990 to 2004 when they were < 18 years of age and had used their device for at least 3 years before replying.

Results: Eighteen implant users responded (14 males), yielding a 60% response rate. Their mean age was 13.3 ± 7.0 years (range 6–17) at implantation and 21.1 ± 3.6 years (range 18–34) when they filled in the questionnaire. Five were attending rabbinical school (yeshiva students), four were in regular military service, five were university students (three also held jobs), two were attending high school, one was employed (and had a university degree), and one had left the yeshiva and was unemployed when he returned the questionnaire. Fourteen respondents use the oral communication mode for conversation and the other 4 use both oral and sign languages. Longer daily implant use was significantly associated with coping with the difficulties in the setting in which they were currently active, with a higher level of satisfaction with their current lifestyle and with recognition of the implant’s contribution to this satisfaction (P = 0.037, P = 0.019 and P = 0.001, respectively).

Conclusions: Advances in cochlear implant technologies enable profoundly deaf implanted children to integrate well into the Israeli hearing society, albeit with a large inter-subject variability.

Pancreatic cancer is not a common malignancy in Israel, but it is the third most common cause of cancer mortality, attributable to a lack of screening tests, inaccessibility of the pancreas, and late cancer stage at diagnosis. We reviewed the epidemiology, known risk factors and screening methods available in Israel and describe the Israeli national consortium that was established to identify persons at risk and decide on screening methods to detect and treat their early-stage pancreatic cancer. In collaboration with the Israel National Cancer Registry, we evaluated the incidence and trends of the disease in the Jewish and non-Jewish populations. The consortium reviewed known lifestyle risk habits and genetic causes, screening methodologies used and available in Israel. Overall, there are about 600 new patients per year, with the highest incidence occurring in Jewish men of European birth (age-standardized rate 8.11/10⁵ for 2003–06). The 5 year survival is about 5%. The consortium concluded that screening will be based on endoscopic ultrasonography. Pancreatic cancer patients and families at risk will be enrolled, demographic and lifestyle data collected and a cancer pedigree generated. Risk factors will be identified and genetic tests performed as required. This concerted national program to identify persons at risk, recommend which environmental risk factors to avoid and treat, and perform endoscopic ultrasound and genetic screening where appropriate, might reduce their incidence of invasive pancreatic cancer and/or improve its prognosis

Background: Tight glucose control has been shown to improve the outcome of patients with severe acute illnesses who are hospitalized in intensive care units and on intravenous insulin-based regimens.

Objectives: To clarify the attitudes of internists towards tight control of glucose levels in acutely ill patients hospitalized in general medical wards.

Methods: A questionnaire on intensive glucose control in acutely ill patients hospitalized in medical wards was mailed to each of the 100 heads of internal medicine departments in Israel.

Results: Fifty physicians responded. Of these, 80% considered tight glucose control to be a major treatment target, but only two-thirds had defined it as a goal in their ward. Furthermore, only about half had a defined protocol for such an intervention. Most physicians considered patients with acute coronary syndrome, stroke and infectious diseases as candidates for a tight glucose control protocol. The most frequently used modalities were multiple blood glucose measurements and repeated injections of short-acting subcutaneous insulin. The main reasons given for not having a defined protocol were lack of guidelines, no evidence of a clear benefit during hospitalization on a medical ward, and a shortage of adequately trained staff.

Conclusions: Inconsistencies in physicians’ attitudes and in treatment protocols regarding tight control of glucose levels in acutely ill patients hospitalized on a medical ward need to be addressed. Evaluation of the feasibility, effectiveness and side effects of a defined protocol is needed before any regimen can be approved by the heads of the internal medicine departments.
 

Background: Although febrile urinary tract infections are very common in young children, the need for antimicrobial prophylaxis and evaluation following a first event is controversial.

Objectives: To assess the approach of leading pediatric specialists throughout Israel.

Methods: A questionnaire regarding the approach to antibiotic prophylaxis and diagnostic evaluation following a first event of febrile UTI[1], according to age and underlying renal abnormality, was sent to all 58 directors of departments of pediatrics, units of pediatric infectious diseases and pediatric nephrology in Israel.

Results: Fifty-six directors (96%) responded. Most prescribed prophylactic antibiotics after UTI. Heads of infectious disease departments prescribed less prophylaxis following UTI at the age of 18 months than heads of pediatrics or heads of pediatric nephrology units (34% vs. 72–75%, P = 0.018), but more often in cases of severe vesico-ureteral reflux without UTI. Cephalosporins were used prophylactically more often by directors of pediatrics compared to heads of pediatric nephrology units (71% vs. 38%, P = 0.048); the latter used non-beta-lactam prophylaxis (61% vs. 23%, P = 0.013) more often. Most pediatricians used renal sonography for evaluation; renal scan was used more commonly by pediatric nephrologists.

Conclusions: The administration of prophylactic antibiotics after UTI is still common practice among pediatric opinion leaders, although the specific approach differs by subspecialty. According to up-to-date evidence-based data, educational efforts are needed to formulate and implement judicious guidelines.

Background: The internet has transformed the patient-physician relationship by empowering patients with information. Because physicians are no longer the primary gatekeepers of medical information, shared decision making is now emerging as the hallmark of the patient-physician relationship.

Objectives: To assess the reactions of primary care physicians to encounters in which patients present information obtained from the internet (e-patients) and to examine the influence of the physicians' personal and demographic characteristics on their degree of satisfaction with e-patients.

Methods: A questionnaire was developed to assess physician attitudes to e-patients, their knowledge and utilization of the internet, and their personal and professional characteristics. Family physicians in central Israel were interviewed by telephone and in person at a continuing medical education course.

Results: Of the 100 physicians contacted by phone, 93 responded to the telephone interviews and 50 physicians responded to the questionnaire in person. There was an 85% response rate. The mean age of respondents was 49 years. Most physicians were born in Israel, with a mean seniority of 22 years. Most had graduated in Eastern Europe, were not board certified and were employees of one of the four health management organizations in Israel. Most physicians responded positively when data from the internet were presented to them by patients (81%). A number of respondents expressed discomfort in such situations (23%). No association was found between physician satisfaction in relationships with patients and comfort with data from the internet presented by patients.

Conclusions: Physicians in this sample responded favorably to patients bringing information obtained online to the consultation. Though it may be difficult to generalize findings from a convenience sample, Israeli family physicians appear to have accepted internet use by patients.