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עמוד בית
Sun, 21.07.24

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September 2012
E. Brauner, J. Kuten, O. Ben-Ishay, D. Hershkovitz and Y. Kluger
August 2012
M. Linder, L. Lev Ari, R. Kurs and Y. Melamed

Background: Patient protection requires the provision of informed consent for participation in medical research. The MacArthur Competence Assessment Tool for Clinical Research (MacCAT-CR) is frequently used for screening the capacity of research subjects to consent to participate in research.

Objectives: To evaluate the utility of the Hebrew translation of the MacCAT-CR for the assessment of capacity of patients with chronic schizophrenia to provide informed consent to participate in clinical trials.

Methods: We evaluated the translated MacCAT-CR by comparing the capacity of patients with chronic schizophrenia to provide informed consent to participate in clinical trials. The following standardized neurocognitive assessment tools were used: Addenbrooke’s Cognitive Examination (ACE) and Frontal Assessment Battery (FAB), as well as the attending doctor’s assessment.

Results: Twenty-one patients participated. Mean MacCAT-CR score was12 ¡À 10.57 (range 0¨C32), mean FAB score was 9.9 ¡À 4.77 (range 1¨C18), mean ACE was 59.14 ¡À 16.6 (range 27¨C86) and mean doctor’s assessment was 5.24 ¡À 1.18 (range 3¨C7).

Conclusions: The Hebrew-version of the MacCAT-CR helped identify patients with the capacity to provide informed consent for participation in research. Patients with FAB scores ¡Ý 12 tended to score higher on the Hebrew-version of the MacCAT-CR, thus confirming the utility of the Hebrew version of the MacCAT-CR. During the screening process for clinical trials it may be practical to administer the concise FAB questionnaire, and then administer the MacCAT-CR only to those who scored ¡Ý 12 on the FAB.

S. Ben Shimol, L. Dukhan, I. Belmaker, S. Bardenstein, D. Sibirsky, C. Barrett and D. Greenberg

Background: Human brucellosis is common in southern Israel among the semi-nomadic Bedouin, a population that consumes unpasteurized dairy products. Though camel milk ingestion is a known mechanism for brucellosis acquisition, only a few reports of sporadic cases have been published in the medical literature.

Objectives: To describe a local brucellosis outbreak in 15 extended Bedouin family members, following ingestion of infected camel milk.

Methods: Data regarding patient’s clinical manifestations, laboratory findings, treatment and outcome were collected from the hospital and the health fund clinics’ computerized database. Camel’s blood and milk were tested for Brucella serology and culture. Cases were defined by positive Rose Bengal test, symptoms correlating with brucellosis, and consumption of infected camel milk.

Results: Fifteen patients were diagnosed with acute brucellosis from March to June 2011. Sixty percent of cases had serum agglutination test titers of 1:160 or higher and 4/8 (50%) had positive blood culture for Brucella melitensis. Arthralgia and fever were the most consistent clinical manifestations. Blood and milk serology and milk culture taken from the female camel were positive for Brucella melitensis.

Conclusions: The treating physicians must consider the possibility of infected camel milk ingestion as the mode of infection, both in sporadic cases and in outbreaks of brucellosis.

R. Eichel, D. Arkadir, S.T. Khoury, A. Werber, S. Kahana-Merhavi, J.M. Gomori, T. Ben-Hur, J.E. Cohen and R.R. Leker
Background: Only 0.5% of stroke patients in Israel are treated with endovascular multi-modal reperfusion therapy (MMRT) each year.

Objectives: To assess our experience with MMRT over the last decade.

Methods: We analyzed data from our stroke registry of patients undergoing MMRT during 2002¨C2011. All patients underwent multi-parametric imaging studies including subtraction angiography according to a predetermined algorithm. Stroke severity was measured with the National Institutes of Health Stroke Scale (NIHSS). Disability was measured with the modified Ranking Scale (mRS) and classified as favorable (mRS ¡Ü 2) or unfavorable. Target vessel recanalization was determined with the thrombolysis in myocardial infarction (TIMI) scale.

Results: During the study period 204 patients were treated 166 of them had complete data sets including mRS scores at 90 days and were included in the analysis. Favorable outcomes at 90 days post-stroke were observed in 37% of patients and the mortality rate was 25%. Patients with favorable outcomes were younger, had significantly lower NIHSS scores on admission and discharge, and more often had complete target vessel recanalization (TIMI 3). On regression analysis the only factor associated with favorable outcome was TIMI 3, whereas increasing age and NIHSS scores on admission and discharge were predictors of poor outcome.

Conclusions: Our data show that MMRT can be successfully implemented in patients with severe stroke in Israel. More than a third of our patients with severe ischemic strokes who could not receive acute treatment were functionally independent after MMRT, demonstrating that this procedure is an important alternative for patients who are not candidates for intravenous tissue plasminogen activator (tPA) or do not achieve recanalization with tPA.
E. Kadmon, D. Menachemi, J. Kusniec, M. Haim, M. Geist and B. Strasberg

Background: The implantable loop recorder (ILR) is an important tool for the evaluation of unexplained syncope, particularly in cases of rarely occurring arrhythmia.

Objectives: To review the clinical experience of two Israeli medical centers with the ILR. Methods: We reviewed the medical records of patients with unexplained syncope evaluated with the ILR at Rabin Medical Center (2006–2010) and Wolfson Medical Center (2000–2009).

Results: The study group included 75 patients (44 males) followed for 11.9 ± 9.5 months after ILR implantation. Patients’ mean age was 64 ± 20 years. The ILR identified an arrhythmic mechanism of syncope in 20 patients (17 bradyarrhythmias, 3 tachyarrhythmias) and excluded arrhythmias in 12, for a diagnostic yield of 42.7%. It was not diagnostic in 17 patients (22.7%) at the time of explant 26 patients (34.7%) were still in follow-up. In two patients ILR results that were initially negative were reversed by later ILR tracings. The patients with bradyarrhythmias included 9 of 16 (56.3%) with surface electrocardiogram conduction disturbances and 2 of 12 (16.7%) with negative findings on carotid sinus massage. All bradyarrhythmic patients received pacemakers the seven patients for whom post-intervention data were available had no or mild symptoms.

Conclusions: The ILR has a high diagnostic yield. Pre-ILR findings correlating with the ILR results are conduction disturbances (positive predictor of arrhythmia) and negative carotid sinus massage results (negative predictor of arrhythmia). Proper patient instruction is necessary to obtain accurate results. Caution is advised when excluding an arrhythmia on the basis of ILR tracings, and long-term follow-up is warranted.

T. Tohami, A. Nagler and N. Amariglio

Chronic myeloid leukemia (CML) is a clonal hematological disease that represents 15–20% of all adult leukemia cases. The study and treatment of CML has contributed pivotal advances to translational medicine and cancer therapy. The discovery that a single chromosomal abnormality, the Philadelphia (Ph) chromosome, is responsible for the etiology of this disease was a milestone for treating and understanding CML. Subsequently, CML became the first disease for which allogeneic bone marrow transplantation is the treatment of choice. Currently, CML is one of the few diseases where treatment targeted against the chromosomal abnormality is the sole frontline therapy for newly diagnosed patients. The use of directed therapy for CML challenged disease monitoring during treatment and led to the development of definitions that document response and predict relapse sooner than the former routine methods. These methods relied on classical cytogenetics through molecular cytogenetics (FISH) and, finally, on molecular monitoring assays. This review discusses the laboratory tools used for diagnosing CML, for monitoring during treatment, and for assessing remission or relapse. The advantages and disadvantages of each test, the common definition of response levels, and the efforts to standardize molecular monitoring for CML patient management are discussed.

S. Bezalel, I. Asher, D. Elbirt and Z.M. Sthoeger

Current treatments for systemic lupus erythematosus (SLE) are effective in reducing morbidity and mortality but are not specific and have severe adverse effects. Based on understanding of the different dysregulated immunological pathways involved in SLE pathogenesis, specific targeted therapies were developed. This review presents the current and the near-future novel biological immune targeted treatments, such as B cell-targeted therapy, cytokine blockade, peptide-based treatments and other novel treatments for SLE.
 

July 2012
I. Potasman, G. Naftali and M. Grupper
Background: Overuse and abuse of antibiotics is a major cause of microbial resistance. Within the hospital setting such overuse necessitates real-time supervision by infectious diseases (ID) specialists.

Objectives: To evaluate the impact of a recently introduced computerized antibiotic authorization system on the pharmacy budget.

Methods: The study was performed in a 400 bed university hospital. With the new system, antibiotic requests are entered electronically by the ward physician and reviewed within minutes to hours by ID specialists. The feedbacks are seen in the wards and pharmacy. Successive years, one before and the other after introduction of the system, were compared.

Results: During the first year with the new system 7167 antibiotic requests were entered 20% of them were rejected, mainly for improper indication (43% of the rejections). During that year the antibiotic expenditure was reduced by 17%, compared to the previous year (~equal to 200,000 US$), and was against the trend of the last 5 years. Of the 35 antibiotics under the control of the ID team, the use of 7 was probably curtailed by the supervision. Pareto analysis revealed that four drugs constituted > 50% of the pharmacy’s expenses. The mortality rate (per 1000 hospitalization days) during those 2 years fell from 4.0 to 3.8.

Conclusions: Computerized antibiotic control by ID specialists is a feasible cost-saving new modality that may help reduce unnecessary antibiotic prescriptions.
R. Marom, R. Lubetzky, F.B. Mimouni, H. Bassan, L. Ben Sira, I. Berger, S. Dollberg and D. Mandel

Background: Infants with severe intraventricular-periventricular hemorrhage (IVH) have higher absolute nucleated red blood cell counts (aNRBC) at birth (a marker of intrauterine hypoxia) than controls. Periventricular leukomalacia (PVL) is known to be associated with prenatal and postnatal events. Whether PVL is also linked to intrauterine hypoxia is unknown.

Objectives: To test the hypothesis that infants with PVL have higher aNRBC counts at birth than controls.

Methods: We studied 14 very low birth weight infants with PVL and compared them with 14 pair-matched controls without PVL. Head ultrasound scans were performed in all infants on days 3–5 and 21–25 of life. Paired tests, Fisher exact tests and stepwise logistic regression were performed for analysis.

Results: Groups were similar for gestational age (GA), birth weight (BW), prolonged rupture of membranes (PROM), Apgar scores, IVH, and aNRBC counts. PVL correlated significantly with low partial pressure of CO2 (pCO2) and IVH (P < 0.01). In logistic regression, when GA, gender, PROM, antenatal steroid therapy, 1 (or 5) minute Apgar scores, IVH grade, nosocomial sepsis, patent ductus arteriosus, necrotizing enterocolitis (NEC), need for pressors, aNRBC counts and lowest pCO2 were used as independent variables, pCO2 (P = 0.002), IVH grade (P = 0.001), GA (P = 0.038), NEC (P = 0.061) and use of dopamine (P = 0.010) remained in the analysis (total R2 = 68.2%).

Conclusions: In contrast to severe IVH, aNRBC counts do not predict the development of PVL.

E. Baharav and A. Weinberger
Background: The human lymphocyte antigen (HLA) molecule B*5101 is a functioning receptor of the immune system and is generally accepted as a genetic marker for Behçet disease (BD), a multi-organ, chronic inflammatory disorder. The role of the HLA-B*5101 in the pathogenesis of BD is elusive. The assumption that HLA-B*5101 has an active role in BD is suggestive, but no antigen has yet been identified.

Objectives: To evaluate the potential binding capacity of various antigens to the HLA-B*5101 molecule.

Methods: Using bioinformatics programs, we studied the binding capacity of HLA-B*5101 and its corresponding rat molecule RT.A1 to the following antigens: heat shock protein-60 (HSP-60), major histocompatibility complex class I chain-related gene A (MICA), retinal S-antigen (S-Ag), HLA-B-27 molecule and its peptide (PD) and tropomyosin (TPM), all of which serve as antigens in animal models corresponding to BD.

Results: In each protein including the B*5101 molecule itself, the computerized programs revealed several short sequences with potential high binding capacity to HLA-B*5101 with the exception of B-27PD. The rat MHC RT1.Al had no binding capacity to S-Ag.

Conclusions: The evaluated proteins have the potential to bind to and to serve as potential antigens to the HLA-B*5101 and the rat MHC RT1.Al molecules. The pathogenicity of these suggested short peptides should be evaluated in animal models of BD.
N. Shapira

The Israeli Paradox“ (1996) of low national health rankings despite adequate diet – attributed to high dietary n-6 polyunsaturated fatty acids (PUFA) – coincided with long-observed dichotomies between women’s worse international status vs. men’s advantage. This raised the assumption of a gender link to high n-6 risk as an explanation for both national phenomena. Israeli women’s disadvantage was shown by worse international rankings, i.e., life expectancy (LE), 11th vs. men’s 3rd-best/22 countries (2000), and 14th vs. 6th/34 (2010) all-cause and all-cancer mortality both 15th vs. 2nd-best/22 (2000), and 15th vs. 6th/22 and 12th vs. 2nd-best/22 (2010). Breast cancer mortality rates were +21.8%, vs. prostate -30.4%, compared to Eur-A (27 country) averages (2005). Gender gaps/ratios were smaller than European Union-15, i.e., LE at birth by 34.4–26.4% (2000–2010), respectively, and at 65 years 45.9–35.3% all-cause mortality by 43.3–33.4%, and all-cancer 65.2–58.7%. The Israeli diet was mostly close to guidelines, but n-6 intake (10–12% kcal) was much higher than both recommended and traditional Mediterranean diet“ levels. Research showing females’ greater potential for conversion of PUFA to long-chain PUFA (LCPUFA) may suggest their potentially increased production of n-6 eicosanoids with known pro-inflammatory/oxidative/carcinogenic potential. An N-6 Gender Nutrition Paradox“ hypothesis is suggested here, for the first time, associating women’s higher risk and lead in the national paradox“ with greater potential for n-6 conversion to pro-inflammatory/oxidative/carcinogenic eicosanoids compared to men. This may also exacerbate women’s risk associated with genetic predisposition (i.e., BRCA) and/or sociopolitical stress. Global abandonment of traditional diets/foods together with increasing n-6 consumption and western disease rates emphasize the importance of considering gender in nutritional epidemiology and preventive strategies.

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