Netanya, Israel
Netanya, Israel

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Markowitz S.Y.,Laniado Hospital | Baron E.P.,Cleveland Clinic | Hentz J.G.,Mayo Medical School | Kalidas K.,University of South Florida | And 4 more authors.
Headache | Year: 2014

Objective To identify factors associated with triptan discontinuation among migraine patients. Background It is unclear why many migraine patients who are prescribed triptans discontinue this treatment. This study investigated correlates of triptan discontinuation with a focus on potentially modifiable factors to improve compliance. Methods This multicenter cross-sectional survey (n = 276) was performed at US tertiary care headache clinics. Headache fellows who were members of the American Headache Society Headache Fellows Research Consortium recruited episodic and chronic migraine patients who were current triptan users (use within prior 3 months and for ≥1 year) or past triptan users (no use within 6 months; prior use within 2 years). Univariate analyses were first completed to compare current triptan users to past users for: migraine characteristics, other migraine treatments, triptan education, triptan efficacy, triptan side effects, type of prescribing provider, Migraine Disability Assessment (MIDAS) scores and Beck Depression Inventory (BDI) scores. Then, a multivariable logistic regression model was selected from all possible combinations of predictor variables to determine the factors that best correlated with triptan discontinuation. Results Compared with those still using triptans (n = 207), those who had discontinued use (n = 69) had higher rates of medication overuse (30 vs 18%, P =.04) and were more likely to have ever used opioids for migraine treatment (57 vs 38%, P =.006) as well as higher MIDAS (mean 63 vs 37, P =.001) and BDI scores (mean 10.4 vs 7.4, P =.009). Compared with discontinued users, current triptan users were more likely to have had their triptan prescribed by a specialist (neurologist, headache specialist, or pain specialist) (74 vs 54%, P =.002) and were more likely to report headache resolution (53 vs 14%, P <.001) or a reduction in pain intensity (71 vs 28%, P <.001) most of the time from their triptan. On a 1-5 scale (1 = disagree, 5 = agree), triptan users felt they had more: control over their migraine attacks (2.9 vs 2.1), confidence in their prescribing provider (4.5 vs 4.0), and were more educated about triptan use (4.2 vs 3.7) compared with triptan discontinuers (P <.001 for all comparisons). Although both current and prior users reported similar rates of side effects (48 vs 43%, P =.44), of those who discontinued use, the main reasons were for lack of effect (44%) and side effects (29%). Our multivariable modeling revealed that the strongest correlate of triptan discontinuation was lack of efficacy (odds ratio = 17, 95% confidence interval [8.8, 33.0]). Other factors associated with discontinuation included MIDAS > 24 (2.6, [1.5, 4.6]), BDI >4 (2.5, [1.4, 4.5]), and a history of ever using opioids for migraine therapy (2.2, [1.3, 3.8]). Having a triptan prescribed by a specialist and using at least 1 other abortive medication with the triptan were associated with a decreased likelihood of triptan discontinuation (0.41, [0.2-0.7] and 0.44 [0.3, 0.8], respectively). Conclusions As expected, discontinuation was most correlated with lack of efficacy, but other important factors associated with those who had discontinued use included greater migraine-related disability, depression, and the use of opioids for migraine attacks. Compared with patients who had discontinued triptans, current triptan users felt more: educated about their triptan, control over their migraine attacks, and confidence in their prescribing provider. Current triptan users had their triptan prescribed by a specialist and used other abortive medications with their triptan more often compared with patients who had discontinued triptans. Given the cross-sectional nature of this study, we cannot determine if these factors contributed to triptan discontinuation or reflect the impact of such discontinuation. Interventions that address modifiable risk factors for triptan discontinuation may decrease the likelihood of triptan discontinuation and thus improve overall migraine control. Because lack of efficacy was most strongly associated with triptan discontinuation, future research should determine why triptans are effective for some patients but not others. © 2013 American Headache Society.


Yaakov K.B.,Tel Aviv University | Gershoni-Emek N.,Tel Aviv University | Bulvik S.,Laniado Hospital | Kassis I.,Hadassah Medical Organization | And 2 more authors.
Human Molecular Genetics | Year: 2013

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder of motor neurons. Although most cases of ALS are sporadic (sALS) and of unknown etiology, there are also inherited familial ALS (fALS) cases that share a phenotype similar to sALS pathological and clinical phenotype. In this study, we have identified two new potential genetic ALS biomarkers in human bone marrow mesenchymal stem cells (hMSC) obtained from sALS patients, namely the TDP-43 (TAR DNA-binding protein 43) and SLPI (secretory leukocyte protease inhibitor). Together with the previously discovered ones-CyFIP2 and RbBP9, we investigated whether these four potential ALS biomarkers may be differentially expressed in tissues obtained from mutant SOD1G93A transgenic mice, a model that is relevant for at least 20% of the fALS cases. Quantitative real-time PCR analysis of brain, spinal cord and muscle tissues of the mSOD1G93A and controls at various time points during the progression of the neurological disease showed differential expression of the four identified biomarkers in correlation with (i) the tissue type, (ii) the stage of the disease and (iii) the gender of the animals, creating thus a novel spatiotemporal molecular signature of ALS. The biomarkers detected in the fALS animal model were homologous to those that were identified in hMSC of our sALS cases. These results support the possibility of a molecular link between sALS and fALS and may indicate common pathogenetic mechanisms involved in both types of ALS. Moreover, these results may pave the path for using the mSOD1G93A mouse model and these biomarkers as molecular beacons to evaluate the effects of novel drugs/treatments in ALS. © The Author 2013.


Solmesky L.,Tel Aviv University | Lefler S.,Tel Aviv University | Jacob-Hirsch J.,Cancer Research Center | Bulvik S.,Laniado Hospital | And 2 more authors.
PLoS ONE | Year: 2010

Human mesenchymal stem cells (hMSC) are easily isolated from the bone marrow by adherence to plastic surfaces. These cells show self-renewal capacity and multipotency. A unique feature of hMSC is their capacity to survive without serum. Under this condition hMSC neither proliferate nor differentiate but maintain their biological properties unaffected. Therefore, this should be a perfect platform to study the biological effects of defined molecules on these human stem cells. We show that hMSC treated for five days with retinoic acid (RA) in the absence of serum undergo several transcriptional changes causing an inhibition of ERK related pathways. We found that RA induces the loss of hMSC properties such as differentiation potential to either osteoblasts or adipocytes. We also found that RA inhibits cell cycle progression in the presence of proliferating signals such as epidermal growth factor (EGF) combined with basic fibroblast growth factor (bFGF). In the same manner, RA showed to cause a reduction in cell adhesion and cell migration. In contrast to these results, the addition of EGF+bFGF to serum free cultures was enough to upregulate ERK activity and induce hMSC proliferation and cell migration. Furthermore, the addition of these factors to differentiation specific media instead of serum was enough to induce either osteogenesis or adipogenesis. Altogether, our results show that hMSC's ability to survive without serum enables the identification of signaling factors and pathways that are involved in their stem cell biological characteristics without possible serum interferences. © 2010 Solmesky et al.


Bental Y.,Laniado Hospital | Bental Y.,Technion - Israel Institute of Technology | Reichman B.,Gertner Institute | Reichman B.,Tel Aviv University | And 6 more authors.
Pediatrics | Year: 2011

OBJECTIVE: We hypothesized that maternal diabetes mellitus (DM) increases the risk for mortality, respiratory distress syndrome (RDS), and major complications of prematurity. METHODS: Analysis of prospectively collected (1995-2007) Israel National Very Low Birth Weight Infant Database. Maternal DM was recorded as pregestational or gestational. Multivariable logistic regression analysis was used to assess the independent effect of maternal DM status on infant mortality, RDS, and other complications of prematurity. RESULTS: Infants of mothers with pregestational (n = 120) and gestational (n = 825) DM were similar, and their data were pooled for analyses. Mothers with DM were more likely to have received a complete course of prenatal steroids than control mothers. Infants of diabetic mothers (IDM) had a slightly higher gestational age and birthweight than non-IDM's. Distribution of birthweight percentiles and the mean birthweight z scores were similar. Apgar scores were statistically higher in the IDM group. There were no significant differences between the 2 groups in terms of delivery room mortality, RDS, and other major complications of prematurity. Total mortality and bronchopulmonary dysplasia rates were significantly higher in the nondiabetic group. The adjusted odds ratios for mortality, RDS, bronchopulmonary dysplasia, intraventricular hemorrhage, periventricular leukomalacia, retinopathy of prematurity, necrotizing enterocolitis, and patent ductus arteriosus were not significantly increased in the IDM group. CONCLUSIONS: With modern management and adequate prenatal care, IDM born very low birthweight do not seem to be at an excess risk of developing RDS or other major complications of prematurity compared with non-IDM. Copyright © 2011 by the American Academy of Pediatrics.


Shimoni Z.,Laniado Hospital | Rodrig J.,Laniado Hospital | Kamma N.,Laniado Hospital | Froom P.,Tel Aviv University
BMJ Open | Year: 2012

Objectives: To determine if more restrictive indications for urinary catheterisation reinforced by daily chart review will lower catheterisation rates. Design: An historical comparative observational study. Setting: An internal medicine department in a regional hospital in Israel. Participants: The authors compared 882 patients hospitalised after a change in policy to an historical cohort of 690 hospitalised patients. Exclusions included patients less than age 30 and those with bladder outlet obstruction. Intervention: Emergency and internal medicine department physicians received instruction on a more restricted urinary catheterisation policy. During daily chart rounds, admissions were discussed with an emphasis on the appropriateness of all new urinary catheter insertions. Main outcome measures: The primary outcome measure was catheterisation rate by admission diagnosis. Secondary outcome measures were the need for post-admission in hospital catheterisations and the rate of indwelling catheters 14 or more days after discharge. Results: There was a reduction in catheterisation rate in patients with congestive heart failure from 30/106 (29.3%) to 3/107 (2.8%) (p<0.001), in patients with an admission diagnosis of fever unable to provide a urine sample for culture from 35/132 (26.5%) to 12/153 (7.8%) (p<0.001) and in patients admitted for palliative care from 51.7% (15/29) to 12.0% (3/25) (p=0.002). The overall rate of catheterisation decreased from 17.5% (121/690) to 6.6% (58/882) (p<0.001). There was only one indicated catheterisation after admission due to the change in policy, and the proportion of patients discharged with catheters decreased. Conclusion: The use of more restrictive indications for urinary catheterisation along with daily chart rounds can reduce the rate of urinary catheterisation in an internal medicine department without adverse consequences.


Shimoni Z.,Laniado Hospital | Froom P.,Tel Aviv University
Expert Review of Anti-Infective Therapy | Year: 2015

This review summarizes expert opinion and evidence on the diagnosis, treatment and prevention of trichinellosis. Laboratory test results are not sufficiently sensitive for the diagnosis of individual patients when outbreaks are suspected. A likely diagnosis depends on identifying a potential common source of exposure supported by detection of antibodies to Trichinella antigens in a higher than expected proportion of exposed patients. Expert opinion is discordant, but for patients with symptomatic disease, there are theoretical reasons to recommend treatment with albendazole (rather than mebendazole) taken with fatty meals and prednisone. Education of the public is probably not a reliable way to prevent trichinellosis and when feasible should be augmented with mandatory testing of all potentially infected meat. © 2015 © Informa UK, Ltd.


Nachmany H.,Tel Aviv University | Wald S.,Tel Aviv University | Abekasis M.,Tel Aviv University | Bulvik S.,Laniado Hospital | Weil M.,Tel Aviv University
Disease Markers | Year: 2012

Amyotrophic lateral sclerosis (ALS) is a fatal, neurodegenerative disorder caused by degeneration of motor neurons. The cause for most cases of ALS is multi-factorial,this enhances the need to characterize and isolate specific biomarkers found in biological samples from ALS patients. To this end we use human mesenchymal stem cells (hMSC) derived from the bone marrow of six ALS patients (ALS hMSC) and identified two genes, Cytoplasmic FMR Interacting Protein 2 (CyFIP2) and Retinoblastoma (Rb) Binding Protein 9 (RbBP9) with a significant decrease in post transcriptional A to I RNA editing compared to hMSC of healthy individuals. At the transcriptional level we show abnormal expression of these two genes in ALS hMSC by quantitative real time-PCR (qRT-PCR) and Western blot suggesting a problem in the regulation of these genes in ALS. To strengthen this view we tested by qRT-PCR the expression of these genes in peripheral blood leukocytes (PBL) isolated from blood samples of 17 ALS patients and found that CyFIP2 and RbBP9 levels of expression were significantly different compared to the levels of expression of these two genes in 19 normal PBL samples. Altogether we found two novel ALS potential biomarkers in non-neural tissues from ALS patients that may have direct diagnostic and therapeutic implications to the disease. © 2012 - IOS Press and the authors. All rights reserved.


Czernobilsky B.,Patho Laboratory Diagnostics | Lifschitz-Mercer B.,Institute of Pathology | Trejo L.,Patho Laboratory Diagnostics | Atlas I.,Laniado Hospital
International Journal of Surgical Pathology | Year: 2011

This is a report of a paratubal adult granulosa cell tumor (GCT) located within the right broad ligament in a 62-year-old woman. These are rare tumors with only 8 cases reported so far. Because of an overlap of topographic, morphologic, and immunohistochemical features, it is not always possible to differentiate between the broad ligament GCT and female adnexal tumor of probable Wolffian origin (FATWO). Although nuclear grooving is not an exclusive feature of GCT and can be seen in a variety of other neoplasms, in the context of the differential diagnosis between broad ligament GCT and FATWO, the presence of this feature may be very useful in establishing the diagnosis of broad ligament GCT. © SAGE Publications 2011.


Summary: Diabetes is a multisystem disorder. Diabetes care is a multidisciplinary process. The Bildirici Center for Diabetes Care and Research opened its doors to its first patients in August 2007, as the first center in Israel to offer comprehensive integrated multidisciplinary care for people with diabetes. In addition to direct patient care, the Center has organized courses, lectures and workshops for people with diabetes, as well as for professionals caring for people with diabetes and for the general community. The ability of individuals within different departments to develop and implement such a center may have been facilitated by the smallness of our institution and the familiarity they share as a result. We have shown how a community hospital, without ties to a major medical center or academic institution, can establish a multidisciplinary inpatient and outpatient diabetes center, the first of its kind in a country. © 2012 John Wiley & Sons, Ltd.


Boner G.,Laniado Hospital
Diabetes/Metabolism Research and Reviews | Year: 2011

Diabetes mellitus and its complications are major causes of morbidity and mortality. Traditionally hypertension and poor diabetic control have been considered to be major risk factors for the development of cardiac involvement. This review will examine two novel risk factors, namely renal involvement and left ventricular hypertrophy. Renal involvement is manifested by increased excretion of protein in the urine and/or decreasing renal function. Several large studies have shown that both these factors are significant risk factors for cardiac involvement and increased mortality both in diabetic and non-diabetic subjects. There is strong evidence to suggest an association between renal and cardiac involvement. Cardiac hypertrophy is an important risk factor for the development of cardiac involvement. It is generally assumed that ventricular hypertrophy is a result of hypertension. However, it has been shown to be associated with metabolic disorders such as central obesity, diabetes mellitus and hypercholesterolemia, even in the absence of hypertension. The prevalence of ventricular hypertrophy is increased in patients with diabetes mellitus, especially in the presence of renal involvement. Diabetic patients with renal involvement and cardiac hypertrophy have also been shown to have an increased risk for developing cardiac complications and having an increased mortality rate. Thus these two risk factors are important in the prognosis of the diabetic patient. Follow-up of the diabetic patient should include careful examination for the presence of proteinuria, reduced renal function and left ventricular hypertrophy in the hope that treatment of these factors may reduce morbidity and mortality. © 2011 John Wiley & Sons, Ltd.

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