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עמוד בית
Mon, 17.06.24

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November 2022
Regev Landau MD, Ana Belkin MD, Sapir Kon-Kfir MD, Nira Koren-Morag PhD, Avishay Grupper MD, David Shimunov MD, Ben-Ami Sela PhD, Ehud Grossman MD, Gadi Shlomai MD, Avshalom Leibowitz MD

Background: Most dyspneic patients in internal medicine departments have co-morbidities that interfere with the clinical diagnosis. The role of brain natriuretic peptide (BNP) levels is well-established in the acute setting but not in hospitalized patients.

Objectives: To evaluate the additive value of BNP tests in patients with dyspnea admitted to medical wards who did not respond to initial treatment.

Methods: We searched the records of patients who were hospitalized in the department of internal medicine D at Sheba Medical Center during 2012 and were tested for BNP in the ward. Data collected included co-morbidity, medical treatments, diagnosis at presentation and discharge, lab results including BNP, re-hospitalization, and mortality at one year following hospitalization.

Results: BNP results were found for 169 patients. BNP was taken 1.7 ± 2.7 days after hospitalization. According to BNP levels, dividing the patients into tertiles revealed three equally distributed groups with a distinctive character. The higher tertile was associated with higher rates of cardiac co-morbidities, including heart failure, but not chronic obstructive pulmonary disease. Higher BNP levels were related to one-year re-hospitalization and mortality. In addition, higher BNP levels were associated with higher rates of in-admission diagnosis change.

Conclusions: BNP levels during hospitalization in internal medicine wards are significantly related to cardiac illness, the existence of heart failure, and patient prognosis. Thus, BNP can be a useful tool in managing dyspneic patients in this setting.

November 2019
Agata Schlesinger MD, Avraham Weiss MD, Olga Nenaydenko MD, Nira Koren-Morag PhD, Abraham Adunsky MD and Yichayaou Beloosesky MD, MHA

Background: Statins and selective serotonin reuptake inhibitors (SSRIs) have beneficial effects on health outcomes in the general population. Their effect on survival in debilitated nursing home residents is unknown.

Objectives: To assess the relationships between statins, SSRIs, and survival of nursing home residents.

Methods: Baseline patient characteristics, including chronic medications, were recorded. The association of 5-year survival with different variables was analyzed. A sub-group analysis of survival was performed according to baseline treatment with statins and/or SSRIs.

Results: The study comprised 993 residents from 6 nursing homes. Of them, 285 were males (29%), 750 (75%) were fully dependent, and 243 (25%) were mobile demented. Mean age was 85 ± 7.6 years (range 65–108). After 5 years follow-up, the mortality rate was 81%. Analysis by sub-groups showed longer survival among older adults treated with only statins (hazard ratio [HR] for death 0.68, 95% confidence intervals [95%CI] 0.49–0.94) or only SSRIs (HR 0.6, 95%CI 0.45–0.81), with the longest survival among those taking both statins and SSRIs (HR 0.41, 95%CI 0.25–0.67) and shortest among residents not taking statins or SSRIs (P < 0.001). The survival benefit remained significant after adjusting for age and after conducting a multivariate analysis adjusted for sex, functional status, body mass index, mini-mental state examination, feeding status, arrhythmia, diabetes mellitus, chronic kidney disease, and hemato-oncological diagnosis.

Conclusion: Treatment with statins and/or SSRIs at baseline was associated with longer survival in debilitated nursing home residents and should not be deprived from these patients, if medically indicated. 

September 2017
Marianna Rachmiel MD, Larisa Naugolni MD, Kineret Mazor-Aronovitch MD, Nira Koren-Morag PhD and Tzvi Bistritzer MD

Background: Bone maturation is currently assessed by subjective and automated radiography. 

Objectives: To evaluate the concordance and reproducibility of a quantitative ultrasound (QUS) based device versus X-ray based methods.

Methods: The study population comprised 150 children, 76 males, 4–17 years of age. X-ray scans were evaluated according to wrist, carpal and phalanx areas for bone age. QUS was performed by the the BAUS™ device (SonicBone, Rishon Lezion, Israel), using speed-of-sound (SOS) and distance attenuation factor (ATN) in similar areas. Data from 100 subjects were used to establish the device conversion equation, and 50 measurements were assigned to assess inter-modality agreement. 

Results: BAUS showed high repeatability performance, 0.73% relative standard deviation for SOS and 3.5% for ATN. R2 for the conversion equation, including gender, SOS, and ATN, was 0.80 for all methods (P < 0.001). There was no significant bias in bone age assessments.

Conclusions: Bone age assessment by SonicBone is comparable to the assessment by X-ray based methods. 

 

July 2014
Michael Arad MD, Tamar Nussbaum MD, Ido Blechman BA, Micha S. Feinberg MD, Nira Koren-Morag PhD,Yael Peled MD and Dov Freimark MD

Background: Contemporary therapies improve prognosis and may restore left ventricular (LV) size and function.

Objectives: To examine the prevalence, clinical features and therapies associated with reverse remodeling (RR) in dilated cardiomyopathy (DCM).

Methods: The study group comprised 188 DCM patients who had undergone two echo examinations at least 6 months apart. RR was defined as increased LV ejection fraction (LVEF) by ≥ 10% concomitant with ≥ 10% decreased LV end-diastolic dimension.

Results: RR occurred in 50 patients (26%) and was associated with significantly reduced end-systolic dimension, left atrial size, grade of mitral regurgitation, and pulmonary artery pressure. NYHA class improved in the RR group. RR was less common in familial DCM and a long-standing disease and was more prevalent in patients with prior exposure to chemotherapy. Recent-onset disease, lower initial LVEF and normal electrocardiogram were identified as independent predictors of RR. Beta-blocker dose was related to improved LVEF but not to RR. Over a mean follow-up of 23 months, 16 patients (12%) from the 'no-RR' group died or underwent heart transplantation compared to none from the RR group (P < 0.01).

Conclusions: Contemporary therapies led to an an improvement in the condition of a considerable number of DCM patients. A period of close observation while optimizing medical therapy should be considered before deciding on invasive procedures. 

July 2008
A. Mager, N. Koren-Morag, M. Shohat, A. Dadashev, R. Kornowski, A. Battler and D. Hasdai

Background: The C677T mutation in the methylenetetrahydrofolate reductase (MTHFR) gene is associated with early onset of coronary artery disease in some populations with certain ethnic backgrounds. However, data on its effect on CAD[1] development in women are limited and conflicting.

Objectives: To investigate the effects of the MTHFR C677T mutation and ethnicity on the development and age at onset of CAD in women in Israel.

Methods: The sample included 135 Jewish women with well-documented CAD (62 Ashkenazi, 44 Oriental and 29 of other origins) in whom CAD symptoms first developed at age ≤ 65 years. DNA samples from 235 women served as the control.

Results: CAD symptoms developed later in Ashkenazi than in Oriental women or women of other origins (51.0 ± 7.0 years vs. 48.3 ± 7.5 and 46.3 ± 7.7 years, respectively, P = 0.024). Among Ashkenazi women, the T/T genotype was less common in patients in whom CAD symptoms appeared after age 50 (6.4%) than in patients with earlier CAD symptoms (25.8%, P = 0.037) and Ashkenazi control subjects (23.3%, P = 0.045). Among women from other origins, these differences were not significant. On logistic regression analysis, the T/T genotype was associated with a nearly fourfold increase in the risk of early onset (age < 50 years) of CAD (odds ratio 3.87, 95% confidence interval 1.12–13.45, adjusted for risk factors and origin) and a trend towards an influence of ethnicity (P = 0.08). Compared to Ashkenazi women, the risk of early development of CAD associated with the T/T genotype among Oriental ones was 0.46 (95%CI[2] 0.189–1.114) and in women of other origins, 5.84 (95%CI 1.76–19.34). Each additional risk factor increased the risk of earlier onset of CAD by 42% (OR[3] 1.42, 95%CI 1.06–1.89).

Conclusions: The age at onset of CAD in Israeli women is influenced by the MTHFR genotype, ethnic origin and coronary risk factors.






[1] CAD = coronary artery disease

[2] CI = confidence interval

[3] OR = odds ratio


January 2006
D. Tanne, U. Goldbourt, S. Koton, E. Grossman, N. Koren-Morag, M. S. Green and N. M. Bornstein

Background: There are no national data on the burden and management of acute cerebrovascular disease in Israel.

Objectives: To delineate the burden, characteristics, management and outcomes of hospitalized patients with acute cerebrovascular disease in Israel, and to examine adherence to current guidelines.

Methods: We prospectively performed a national survey in all 28 hospitals in Israel admitting patients with acute cerebrovascular events (stroke or transient ischemic attacks) during February and March 2004.

Results: During the survey period 2,174 patients were admitted with acute cerebrovascular disease (mean age 71 ± 13 years, 47% women; 89% ischemic stroke or TIA[1], 7% intracerebral hemorrhage and 4% undetermined stroke). Sixty-two percent of patients were admitted to departments of Medicine and a third to Neurology, of which only 7% were admitted to departments with a designated stroke unit. Head computed tomography was performed during hospitalization in 93% of patients. The overall rate of urgent thrombolytic therapy for acute ischemic stroke was 0.5%. Among patients with ischemic stroke or TIA, 94% were prescribed an antithrombotic medication at hospital discharge, and among those with atrial fibrillation about half were prescribed warfarin. Carotid duplex was performed in 30% and any vascular imaging study in 36% of patients with ischemic events. The mean length of hospital stay was 12 ± 27 days for ICH[2] and 8 ± 11 days for ischemic stroke. Among patients with ICH, 28% died and 66% died or had severe disability at hospital discharge, and for ischemic stroke the corresponding rates were 7% and 41% respectively. Mortality rates within 3 months were 34% for ICH and 14% for ischemic stroke.

Conclusions: This national survey demonstrates the high burden of acute stroke in Israel and reveals discordance between existing guidelines and current practice. The findings highlight important areas for which reorganization is imperative for patients afflicted with acute stroke.






[1] TIA = transient ischemic attack

[2] ICH = intracerebral hemorrhage


May 2002
Michael Eckstein, MSc, Iris Vered, MD, Sophia Ish-Shalom, MD, Anat Ben Shlomo, MD, Avraham Shtriker, MD, Nira Koren-Morag, PhD and Eitan Friedman, MD, PhD

Background: Genetic factors have been shown to play a major role in the development of peak bone mass, with hereditability accounting for about 50-85% of the variance in bone mass. Numerous candidate genes were proposed to be involved in osteoporosis, but the precise genes and their relative contribution remain unknown.

Objectives: To gain insight into the genetic basis of idiopathic low bone mineral density in Israeli patients by analyzing the impact of two candidate genes: polymorphism of the vitamin D receptor gene and polymorphism A986s in the calcium-sensing receptor gene.

Methods: We analyzed 86 Jewish Israeli patients with LBMD[1]: 38 premenopausal women and 48 men, and compared the allelic pattern distribution with that of the general population (126 men and 112 women). Genotyping of the VDR[2] gene was performed in three polymorphic sites using restriction enzymes, and allelic analysis of A986s polymorphism in the CaSR[3] gene was performed using the denaturing gradient gel electrophoresis technique.  

Reaults: In LBMD women the distributions of VDR alleres in Apal polymorphism were AA=7/28, Aa=16/28 and aa=5/28; in TaqI polymorphism TT=10/31, Tt=16/31 and tt=5/31; and in BsmI polymorphism BB=7/32, Bb=14/32 and 11/32. In LBMD men the distributions were AA=17/39, Aa=21/39 and aa=1/39; in TaqI polymorphism TT=12/42, Tt=23/42 and tt=7/42; and in BsmI polymorphism BB=12/41 Bb=18/41 and bb=11/41. The distributions of all these polymorphisms in the control groups were not significantly different. Adjusting for the independent age and gender parameters confirmed that these three polymorphisms of the VDR gene did not have a significant effect on bone mineral density. Thirty percent (24/79) of LBMD patients of either sex displayed heterozygosity of the CaSR A986s polymorphism, compared with 40 of 203 controls (19.7%) (P=0.059). Adjusting for age and gender in these patients revealed a significant difference in the femoral neck BMD[4] between homozygotes and heterozygotes (P=0.002). The age at menarche of the LBMD women was found to predict 61% of the variance of femoral neck BMD.

Conclusions: In Israeli Jewish men and premenopausal women VDR gene alleles do not seem to be associated with lower lumbar spine or femoral neck BMD. A trend towards heterozygosity for a CaSR polymorphism missense mutation was noted in the LBMD patients. Age at menarche in the LBMD women was found to be an important predictor of BMD. A significant difference was found between LBMD women and healthy control women towards heterozygosity for a CaSR polymorphism, as well between homozygotes and heterozygotes for a CaSR polymorphism in BMD. The significance of these findings and their applicability to a larger population awaits further studies.

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[1] LBMD = low bone mineral density


[2] VDR = vitamin D receptor


[3] CaSR = calcium-sensing receptor


[4] BMD = bone mineral density




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