Israel Medical Association Journal

Background: The incidence of stroke varies among ethnically and culturally diverse groups.

Objectives: To examine the ethnic-geographic patterns of stroke incidence in men and women with coronary heart disease in Israel, focusing on the extent to which this variability can be explained by known differences in risk factors for stroke.

Methods: Patients with documented coronary heart disease were followed for 6–8 years for incident cerebrovascular events. Baseline medical evaluation included assessment of vascular risk factors and measures of blood lipids. Among 15,052 patients, a total of 1110 were identified with any incident ischemic cerebrovascular event by ICD-9 codes, of whom 613 had confirmed ischemic stroke or transient ischemic attack.

Results: A major excess of ischemic cerebrovascular events among Israeli Arab women as compared to males, and an inverse finding among Israeli born Jews, were noted. The high risk in the Arab population in Israel reflected an unfavorable risk profile, since predicted rates by multivariate analysis and observed rates were 69 and 68 per 1000, respectively. High ischemic cerebrovascular event rates were identified among patients born in the Balkan countries and North Africa (89 and 90 per 1000) but unfavorable risk factor levels of these individuals did not explain them. Most trends appeared similar in male and female patients. A comparison of observed and accepted-according-to-risk-profile rates of ischemic cerebrovascular events yielded significant differences (P = 0.04), consistent with an additional role of geographic/ethnic origin, resulting from factors that remain unrecognized,or with variables unassessed in this study.

Conclusions: We identified an ethnic diversity in stroke risk among Israeli born in different parts of the world beyond what could be expected on the basis of differences in known risk factors. These findings call for detailed research aimed at identifying additional differences in the risk profile of patients with atherothrombotic disease exposed to an increased risk of stroke.
 

Background: Identification of pathogens and their susceptibility to antimicrobials is mandatory for successful empiric antibiotic treatment.

Objectives: To compare the clinical characteristics of patients with bacteremia, as well as the bacterial distribution and antimicrobial susceptibility in community, hospital and long-term care facilities during two periods (2001–2002 and 2005–2006).

Methods: The study was conducted at the HaEmek Medical Center, a community 500-bed teaching hospital in northern Israel serving a population of ~500,000 inhabitants. All episodes of bacteremia (n=1546) during two 2 year periods (2001–2 and 2005–6) were prospectively recorded, evaluated and compared (755 in 2001–2 and 791 in 2005–6).

Results: In both periods the urinary tract was the main port of entry in community and long-term care facility bacteremia, while the urinary tract – primary and catheter-related – were similar in frequency as sources of hospital bacteremia. Escherichia coli was the most frequent pathogen isolate. No significant changes in the frequency of methicillin-resistant Staphylococcus aureus and extended-spectrum beta-lactamase-producing bacteria were seen between the two 2 year periods (2001–2 and 2005–6). The susceptibility of non-ESBL[1]-producing E. coli decreased for some antibiotics while non-ESBL-producing Klebsiella pneumoniae susceptibility profile improved in the same period. A non-statistically significant trend of increased resistance in gram-negative isolates to quinolones, piperacillin and piperacillin-tazobactam was observed, but most isolates still remained highly susceptible to carbapenems. There was a small increase in mortality rate in hospital bacteremia during the second period.

Conclusions: Continuous surveillance is imperative for monitoring the local epidemiology and for developing local treatment guidelines.

Background: Fat tissue mediates the production of inflammatory cytokines and oxidative products, which are key steps in the development of type 2 diabetes and atherosclerosis. Antioxidant-rich diets protect against chronic diseases, but antioxidants may interfere with pro-inflammatory signals.

Objectives: To investigate the effect of the potent tomato-derived antioxidant carotenoid, lycopene, on plasma antioxidants (carotenoids and vitamin E), inflammatory markers (C-reactive protein, interleukin-6, tumor necrosis factor-alpha), and oxidation products (conjugated dienes).

Methods: Eight obese patients (body mass index 37.5 ± 2.5 kg/m²) were compared with a control group of eight lean, age and gender-matched subjects (BMI[1] 21.6 ±  0.6 kg/m²), before and after 4 weeks of lycopene supplementation (tomato-derived Lyc-O-Mato) (30 mg daily).

Results: Plasma carotenoids were significantly reduced in the obese compared to control subjects (0.54 ± 0.06 vs. 0.87 ± 0.08 mg/ml, P < 0.01). CRP[2] levels were significantly higher (6.5 vs. 1.1 mg/L, P = 0.04) in obese vs. controls, as were IL-6[3] and conjugated dienes (3.6 and 7.9-fold, respectively). CRP, IL-6 and conjugated dienes correlated with BMI, while IL-6 and conjugated dienes correlated inversely with carotenoids (P < 0.05). Following lycopene treatment, a significant elevation of plasma carotenoids (1.79 vs. 0.54 ug/ml) and specifically lycopene (1.15 vs 0.23 ug/ml) (P < 0.001) occurred in the treatment vs. placebo group, respectively. Markers of inflammation and oxidation products were not altered by lycopene.
Conclusions: Obese patients showed abnormally higher markers of inflammation and oxidation products and lower plasma carotenoids. The lack of reduction of pro-inflammatory markers could be attributed to the short period of the study and the small number of participants. More studies are needed on the protective qualities of natural antioxidant-rich diets against obesity-related co-morbidities.

Background: High sensitivity C-reactive protein, a marker of inflammation, has been proposed to stratify coronary artery disease risk and is lowered by HMG-CoA reductase (statin) therapy. However, the reproducibility of persistently elevated hs-CRP[1] levels and association with other markers of inflammation in patients with stable CAD[2] on aggressive statin therapy is unknown.

Objectives: To determine the reproducibility of hs-CRP levels measured within 2 weeks in patients with documented CAD with stable symptoms and to identify associations with other markers of inflammation.

Methods: Levels of hs-CRP were measured twice within 14 days (7 ± 4) in 23 patients (22 males and 1 female, average age 66 ± 10 years) with stable CAD and hs-CRP ≥ 2.0 mg/L but ≤ 10 mg/L at visit 1. All patients had received statins for cholesterol management (low density lipoprotein-cholesterol 84 ± 25 mg/dl) with no dose change for > 3 months. None had a history or evidence of malignancy, chronic infection or inflammation, or recent trauma. There was no change in medications between visits 1 and 2, and no patient reported a change in symptoms or general health during this interval. White blood cell count and pro- and anti-inflammatory cytokines were measured at both visits.

Results: hs-CRP levels tended to be lower at visit 2 (median 2.4 mg/L, range 0.8–11 mg/L) than at visit 1 (median 3.3 mg/L, range 2.0–9.7 mg/L; P = 0.1793). However, between the two visits hs-CRP levels decreased by more than 1.0 mg/L in 10 patients and increased by more than 1.0 mg/L in 4 patients. Changes in hs-CRP levels were unrelated to changes in levels of white blood cells (P = 0.4353). Of the cytokines tested, only the anti-inflammatory cytokine interleukin-1 receptor antagonist and the pro-inflammatory cytokine interleukin-8 were above lower limits of detection, but there were no correlations between changes in these values and changes in hs-CRP (both P > 0.5).

Conclusions: In stable CAD patients on aggressive statin therapy, hs-CRP levels may fluctuate over brief periods in the absence of changes in health, cardiac symptom status and medications, and without corroboration with other measures of inflammation. Accordingly, elevated hs-CRP levels should be interpreted with caution in this setting.

Background: Patients with hypertrophic cardiomyopathy are prone to ventricular arrhythmias and sudden death. Identifying patients at risk of sudden death is difficult.

Objectives: To determine whether microvolt T-wave alternans detected during exercise or rapid atrial pacing can identify patients with HCM[1] who are at risk of ventricular arrhythmias and sudden death.

Methods: This prospective observational study included 21 patients with HCM: 11 with hypertrophic obstructive cardiomyopathy, 9 with non-obstructive hypertrophic cardiomyopathy, and 1 with apical hypertrophic cardiomyopathy. TWA[2] was measured while the patients were on anti-arrhythmic medication.

Results: TWA was positive in 9 patients (43%) and negative in 12 (57%). Three patients were resuscitated after sudden death before their enrolment in the study and two patients developed ventricular tachycardia and fibrillation respectively during the study period. After combining the endpoint of sudden death from a ventricular arrhythmia and the presence of ventricular arrhythmias on a Holter monitor, there was no significant correlation between the presence of a positive TWA and the presence of ventricular arrhythmias on the Holter monitor or a history of sudden death.  

Conclusion: TWA cannot be used as a non-invasive test for detecting patients with HCM and electrical instability. TWA is not useful for predicting sudden death in patients with HCM.

Approximately 1 in 31 people suffers from an autoimmune disease. The clinical care of patients with autoimmunity crosses multiple disciplines within pediatrics and internal medicine, including, for example, allergy-clinical immunology, rheumatology, nephrology, hematology, pulmonology and neurology. There are two major areas that are considered in the analysis of autoimmunity in human patients. The first of course is etiology and the second, and of even greater importance, is therapy. Towards that end, considerable attention has focused on the role of hematopoietic stem cell transplantation to either reverse or modulate autoimmune disease. Indeed, it is a field that has far more promise than premise based on a variety of issues, including economics, health care delivery, and obviously efficacy and safety. To put this in perspective, we have attempted to review some of the issues that pertain to this novel approach to the management of autoimmunity. Finally, we emphasize the need to incorporate basic research into therapeutic trials, a vacuum all too often present in clinical intervention.

Background: The predictive value of electrophysiologic studies depends on the aggressiveness of the programmed ventricular stimulation protocol.

Objectives: To assess if non-inducibility with an "aggressive" protocol of PVS[1] identifies post-infarction patients with low ejection fraction (EF[2] ≤ 30%) who may safely be treated without implantable cardioverter defibrillator.

Methods: We studied 154 patients during a 9 year period. Our aggressive PVS protocol included: a) stimulus current five times the diastolic threshold (≤ 3 mA) and b) repetition of double and triple extrastimulation at the shortest coupling intervals that capture the ventricle.

Results: Sustained ventricular tachyarrhythmias were induced in 116 patients (75.4%) and 112 (97%) of them received an ICD[3] (EPS[4]+/ICD+ group). Of the 38 non-inducible patients, 34 (89.5%) did not receive an ICD (EPS-/ICD- group). In comparison to the EPS+/ICD+ group, EPS-/ICD- group patients were older (69 ± 10 vs. 65 ± 10 years, P < 0.05), had a lower EF (23 ± 5% vs. 25 ± 5%,  P < 0.05) and a higher prevalence of left bundle branch block (45.5% vs. 20.2%, P < 0.005). Follow-up was longer for EPS+/ICD+ patients (40 ± 26 months) than for EPS-/ICD- patients (27 ± 22 months) (P = 0.011). Twelve EPS+/ICD+ patients (10.7%) and 5 EPS-/ICD- patients (14.7%) died during follow-up (P = 0.525). Kaplan-Meier survival curves did not show a significant difference between the two groups (P = 0.18).
Conclusions: The mortality rate in patients without inducible VTAs[5] using an aggressive PVS protocol and who did not undergo subsequent ICD implantation is not different from that of patients with inducible arrhythmias who received an ICD. Using this protocol, as many as one-fourth of primary prevention ICD implants could be spared without compromising patient prognosis

Background: Stent thrombosis is a rare but devastating complication of coronary stent implantation. The incidence and potential predictors were assessed in a "real world” single center.

 Objectives: To examine whether socioeconomic status indeed affects the occurrence of stent thrombosis.

Methods: We searched our database for cases of "definite" stent thrombosis (according to the ARC Dublin definitions). Each case was matched by procedure date, age and gender; three cases of stenting did not result in stent thrombosis. Demographic and clinical parameters were compared and socioeconomic status was determined according to a standardized polling and market survey database.

Results: A total of 3401 patients underwent stent implantation in our hospital during the period 2004–2006. Their mean age was 63 ± 11 years, and 80% were males. Twenty-nine cases (0.85%) of “definite” sub-acute/late stent thrombosis were recorded. Mortality at 30 days was recorded in 1 patient (3.5%). Thrombosis occurred 2 days to 3 years after stent implantation. All patients presented with acute myocardial infarction. Premature clopidogrel discontinuation was reported in 60%. Patients with stent thrombosis had significantly higher rates of AMI[1] at the time of the initial procedure (76 vs. 32%, P < 0.001) and were cigarette smokers (60 vs. 28%, P < 0.001). Drug-eluting stents were used less in the stent thrombosis group. There was no difference in stent diameter or length between the two groups. Socioeconomic status was significantly lower at the stent thrombosis group, 3.4 ± 2.4 vs. 5.4 ± 2.6 (mean ± SD, scale 1–10, P < 0.01).

Conclusions: The incidence rate of stent thrombosis is at least 0.85% in our population. It appears in patients with significantly lower socioeconomic status and with certain clinical predictors. These results warrant stricter follow-up and support the policy of healthcare providers regarding patients at risk for stent thrombosis.

Background: Respiratory syncytial virus bronchiolitis is the single leading cause of pediatric admissions for infants in the first year of life, presenting regularly in epidemic proportions in the winter months and impacting in a major way on pediatric inpatient services.

Objective: To quantitate the burden of RSV[1] disease on a pediatric service with the purpose of providing a database for proper health planning and resource allocation.

Methods: We conducted a prospective 5 year study of documented RSV infections in a single pediatric service. RSV disease was confirmed by direct immunofluorescence testing of nasal swabs from all hospitalized cases of bronchiolitis.

Results: On average, 147 ± 17 cases of RSV bronchiolitis were admitted annually in the November–March RSV season, representing 7%–9% of admissions and 10%–14% of hospital days. There was a consistent male preponderance of admissions (55–64%) and 15–23% of admissions were patients less than 1 month old. In peak months RSV cases accounted for as many of 40% of the hospitalized infants and was the leading cause of over-occupancy (up to 126%) in the pediatric ward during the winter,

Conclusions: RSV infection is a major burden for pediatric inpatient services during the winter season. This recurrent and predictable “epidemic,” which regularly leads to over-occupancy, requires increased manpower (nursing) and resources (beds, pulse oximeters) to facilitate proper care. Since this annual event is not a surprise nor an unexpected peak, but rather a cyclical predictable epidemiological phenomenon, proper planning and allocation of services are crucial.