Mical Paul

Tel Aviv University, Tell Afif, Tel Aviv, Israel

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Publications (218)1176.7 Total impact

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    ABSTRACT: Data on the relative efficacy of β-lactam/β-lactamase inhibitors (BL/BLIs) versus carbapenems are scant.
    Journal of Antimicrobial Chemotherapy 09/2014; · 5.34 Impact Factor
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    ABSTRACT: The diagnosis of patients with fever of unknown origin (FUO) remains a challenging medical problem. We aimed to assess the diagnostic contribution of FDG-PET/CT for the evaluation of FUO.
    QJM: monthly journal of the Association of Physicians 09/2014; · 2.36 Impact Factor
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    ABSTRACT: Venous thromboembolism (VTE) is a feared complication during hospitalization. The practice of administering pharmacological prophylaxis is highly endorsed despite failure of studies to show reduction in mortality.
    QJM: monthly journal of the Association of Physicians 09/2014; · 2.36 Impact Factor
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    Leonard Leibovici, Mical Paul
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    ABSTRACT: A recent Cochrane systematic review shook the base of evidence on neuraminidase inhibitors (NIs) claiming that NIs have negligible efficacy in the treatment of influenza(1) . An individual patient data meta-analysis seemingly contradicts these findings(2) . The public, physicians, policy makers and governments are now struggling to understand how to translate these findings to clinical practice. This article is protected by copyright. All rights reserved.
    Clinical Microbiology and Infection 06/2014; · 4.58 Impact Factor
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    I. Oren, M. Paul
    Clinical Microbiology and Infection 06/2014; 20(s6). · 4.58 Impact Factor
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    ABSTRACT: Carbapenem-resistant Gram-negative bacteria (CR-GNB) represent an increasing hazard in healthcare settings. A central question concerning the treatment of invasive infections caused by CR-GNB involves the use of combination therapy. Potential advantages of combination therapy include improved efficacy due to synergy, while the disadvantages include adverse events and increased antibiotic use with a potential drive towards resistance. Several observational studies have examined whether combination therapy offers an advantage over colistin/polymyxin monotherapy. We highlight the inherent limitations of these studies related to their observational design and sample size to show why they do not at present provide an answer to the question of combination versus monotherapy. This distinction is important to guide clinical practice until solid evidence has been obtained and to enable the recruitment of patients into randomized controlled trials. A few randomized controlled trials examining specific combinations have recently been completed or are ongoing. Currently, however, there is no evidence-based support for most combination therapies against CR-GNB, including colistin/carbapenem combination therapy.
    Journal of Antimicrobial Chemotherapy 05/2014; · 5.34 Impact Factor
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    ABSTRACT: Influenza vaccination is recommended for cancer patients, however adherence is low. We aimed to identify predicting factors for vaccination among cancer patients. We conducted a case-control analysis of a patient cohort in the 2010-2011 influenza season. We included adult cancer patients with solid malignancies undergoing chemotherapy and haematological patients with active disease. Patients who died between October-November 2010 (N=43) were excluded from analysis. Cases received the 2011 seasonal influenza vaccine and controls did not. Data were obtained from patients’ records and validated through personal interviews. We collected socio-demographic information, data on the malignancy and co-morbidities and triggers for vaccination and non-vaccination. We performed bivariate and multivariable analyses, in which vaccination status was the dependent variable. Of 806 patients included in analysis, 387 (48%) were vaccinated. Variables associated with vaccination on bivariate analysis were older age, higher socio-economic status, lower crowding-index, marital status (widowed >married >singles), malignancy type (haematological >solid tumours) and time from diagnosis, low-risk malignancy, diabetes, past vaccination, country of birth (non-Russian origin) and physicians’ recommendations. Predicting factors found to be independently associated with vaccination on multivariable analysis were past vaccinations, low-risk malignancy and country of birth. In the analysis conducted among interviewees (N=561), recommendations from the oncologist (OR=10.7 95% CI 5.4-21.2) and from the primary care physician (OR=3.35 95% CI 2.05-5.49) were strong predictors for vaccination. We conclude that “habitual vaccinees” continue influenza vaccinations when ill with cancer. Physicians’ recommendations, especially the oncologist's, have a major influence on patients’ compliance with influenza vaccination.This article is protected by copyright. All rights reserved.
    Clinical Microbiology and Infection 03/2014; · 4.58 Impact Factor
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    ABSTRACT: Patients newly admitted to rehabilitation centres are at high risk for colonization with multidrug-resistant bacteria because many of them have experienced prolonged stays in other healthcare settings and have had high exposure to antibiotics. We conducted a prospective study to determine the prevalence of and risk factors for colonization with extended-spectrum beta-lactamase-producing Enterobacteriaceae (ESBL-PE) in this population. Subjects were screened by rectal swab for ESBL-PE within 2 days of admission. Swabs were plated on chromagar ESBL plates and the presence of ESBL was verified by a central laboratory. A multilevel mixed effects model was used to identify risk factors for ESBL-PE colonization. Of 2873 patients screened, 748 (26.0%) were positive for ESBL-PE. The variables identified as independently associated with ESBL-PE colonization were: recent stay in an acute care hospital for over 2 weeks (OR=1.34, 95% CI: 1.12,1.6), history of colonization with ESBL-PE (OR=2.97, 95% CI: 1.99,-4.43), unconsciousness on admission (OR=2.59, 95% CI: 1.55,4.34), surgery or invasive procedure in the past year (OR= 1.49, 95% CI: 1.2,1.86) and antibiotic treatment in the past month (OR= 1.80, 95% CI: 1.45,2.22). The predictive accuracy of the model was low (area under the ROC curve 0.656). These results indicate that ESBL-PE colonization is common upon admission to rehabilitation centres. Some risk factors for ESBL-PE colonization are similar to those described previously; however, newly identified factors may be specific to rehabilitation populations. The high prevalence and low ability to stratify by risk factors may guide infection control and empiric treatment strategies in rehabilitation settings.This article is protected by copyright. All rights reserved.
    Clinical Microbiology and Infection 03/2014; · 4.58 Impact Factor
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    ABSTRACT: Intravenous (IV) granulocyte colony stimulating factor (G-CSF) might be safer and more convenient than subcutaneous (SC) administration to hospitalized hemato-oncological patients receiving chemotherapy. To compare IV vs. SC G-CSF administration, we conducted a randomized, open-label trial. We included inpatients receiving chemotherapy for acute myeloid leukemia, acute lymphoblastic leukemia, lymphoma or multiple myeloma, and allogeneic or autologous hematopoietic cell transplantation (HCT). Patients were randomized to 5 mcg/kg single daily dose of IV bolus versus SC filgrastim given for its clinical indications. Patients were crossed-over to the alternate study arm on the subsequent chemotherapy course. The primary outcomes were time from initiation of filgrastim to recovery of stable neutrophil count of >500 cells/µL and a composite clinical outcome of infection or death assessed for the first course post-randomization. The study was stopped on the second interim analysis. Of 120 patients randomized, 118 were evaluated in the first treatment course. The mean time to neutropenia resolution was longer with IV G-CSF [7.9 days, 95% confidence interval (CI) 6.6–9.1] compared with SC G-CSF (5.4 days, 95% CI 4.6–6.2), log-rank P = 0.001. Longer neutropenia duration was observed in all patient subgroups, except for patients undergoing autologous HCT. There was no significant difference between groups in the occurrence of infection or death, but more deaths were observed with IV (4/57, 7%) versus SC (1/61, 1.6%) G-CSF administration, P = 0.196. Similar results were observed when all 158 courses following cross-over were analyzed. Patients reported similar pain and satisfaction scores in both groups. Bolus IV administration of G-CSF results in longer neutropenia duration than SC administration, with no difference in clinical or quality-of-life measures. Am. J. Hematol. 89:243–248, 2014. © 2013 Wiley Periodicals, Inc.
    American Journal of Hematology 03/2014; 89(3). · 4.00 Impact Factor
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    ABSTRACT: The study aims were: 1) to define the prevalence of and risk factors for colonization by ESBL-producing Enterobacteriaceae (ESBL-Ent) among healthcare workers (HCWs) and family members (FMs) of ESBL-Ent-colonized patients in rehabilitation units (RUs) and 2) to compare ESBL-Ent isolates from these three groups. The study included 286 FMs of 194 ESBL-Ent-carrying patients identified in 5 RUs located in Israel, Italy, France and Spain. ESBL-Ent were detected by rectal swabs in 26 (9%) of 286 FMs screened. In multivariate analyses, older age of the FM, longer mean number of hours spent with the patient, being a daughter or a female spouse of a patient, and chronic lung disease of the patient were significantly associated with carriage in the FM. Escherichia coli was the most common organism (76%), followed by Klebsiella pneumoniae (19%). Isolates were typed by PFGE and MLST, and ESBLs were identified by PCR-sequencing. A comparison of paired species isolates from FMs and their respective patient showed that 17/23 strains were indistinguishable. ESBL-Ent was detected in 35 (3.5%, E. coli=34) of the 1001 HCWs screened. Feeding patients was associated with ESBL-Ent carriage of HCWs. Only 7 of 23 E. coli subclones cultured from HCWs were also represented among 376 patient-derived ESBL-producing E. coli isolates from the same RUs. In Spain, a higher proportion of HCW and FM were ESBL carriers than elsewhere (p<0.05). In conclusion, the molecular and epidemiological data suggest that FMs are at higher risk of ESBL-Ent acquisition from their relative patients than HCW workers. This article is protected by copyright. All rights reserved.
    Clinical Microbiology and Infection 01/2014; · 4.58 Impact Factor
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    ABSTRACT: The pattern of infections among neutropenic cancer patients has shifted in the last decades to a predominance of Gram-positive infections. Some of these Gram-positive bacteria are increasingly resistant to beta-lactams and necessitate specific antibiotic treatment. To assess the effectiveness of empirical antiGram-positive (antiGP) antibiotic treatment for febrile neutropenic cancer patients in terms of mortality and treatment failure. To assess the rate of resistance development, further infections and adverse events associated with additional antiGP treatment. We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (2013, Issue 7), MEDLINE (1966 to 2013), EMBASE (1982 to 2013), LILACS (1982 to 2013), conference proceedings, and the references of the included studies. First authors of all included and potentially relevant trials were contacted. Randomised controlled trials (RCTs) comparing one antibiotic regimen to the same regimen with the addition of an antiGP antibiotic for the treatment of febrile neutropenic cancer patients. Two review authors independently assessed trial eligibility and risk of bias, and extracted all data. Risk ratios (RR) with 95% confidence intervals (CI) were calculated. A random-effects model was used for all comparisons showing substantial heterogeneity (I(2) > 50%). Outcomes were extracted by intention to treat and the analysis was patient-based whenever possible. Thirteen trials and 2392 patients or episodes were included. Empirical antiGP antibiotics were tested at the onset of treatment in 11 studies, and for persistent fever in two studies. The antiGP treatment was a glycopeptide in nine trials. Seven studies were assessed in the overall mortality comparison and no significant difference was seen between the comparator arms, RR of 0.82 (95% CI 0.56 to 1.20, 852 patients). Ten trials assessed failure, including modifications as failures, while six assessed overall failure disregarding treatment modifications. Failure with modifications was significantly reduced, RR of 0.76 (95% CI 0.68 to 0.85, 1779 patients) while overall failure was the same, RR of 1.00 (95% CI 0.79 to 1.27, 943 patients). Sensitivity analysis for allocation concealment and incomplete outcome data did not change the results. Both mortality and failure did not differ significantly among patients with Gram-positive infections, but the number of studies in the comparisons was small. Data regarding other patient subgroups likely to benefit from antiGP treatment were not available. Glycopeptides did not increase fungal superinfection rates and were associated with a reduction in documented Gram-positive superinfections. Resistant colonisation was not documented in the studies. Current evidence shows that the empirical routine addition of antiGP treatment, namely glycopeptides, does not improve the outcomes of febrile neutropenic patients with cancer.
    Cochrane database of systematic reviews (Online) 01/2014; 1:CD003914. · 5.70 Impact Factor
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    ABSTRACT: Subjective outcomes may exaggerate intervention effects compared to objectively measured outcomes. We compared effect estimates for clinical failure and all-cause mortality clinical trials of antibiotic treatment for pneumonia. A systematic review of randomized controlled trials assessing adults with pneumonia, comparing different antibiotics, published between 2005 and 2012 was undertaken. We compared the intervention to the control arm. The all-cause mortality in the intention-to-treat population and clinical failure as defined by the study investigators for the primary analyzed population were the primary outcomes examined. Risk ratios (RRs) with 95 % confidence intervals (CIs) were pooled, using a fixed effect model. Meta-regression was used to examine the impact of clinical failure on the mortality effect size. Thirty-six trials were included, of which 30 were industry-sponsored and 30 were non-inferiority trials. There was no difference between the effect on mortality for intervention versus control (RR 1.02, 95 % CI 0.91-1.16) and clinical failure (RR 1.01, 95 % CI 0.93-1.10), without significant heterogeneity in both analyses. In double-blind trials with adequate sequence generation and concealment, there was a significant advantage to the intervention for clinical failure (RR 0.86, 95 % CI 0.76-0.98), but not for mortality (RR 0.96, 95 % CI 0.76-1.21). RRs for clinical failure did not explain the variability in the RRs for mortality significantly, with a meta-regression coefficient of 0.32 (95 % CI -0.21-0.85). In non-inferiority trials of antibiotic treatment for pneumonia, we did not find evidence for bias induced by the use of a subjective outcome overall. The small number of trials without sponsorship precludes an adequate assessment of sponsorship effects.
    European Journal of Clinical Microbiology 12/2013; · 3.02 Impact Factor
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    ABSTRACT: As in other disciplines in medicine, systematic reviews (SR) and meta-analyses (MA) in infectious diseases are an important aid to clinical decision making. In the present article we review features important to SRs in infectious diseases that should be addressed in most SRs and MAs. We stress the need to include in the SR analysis all patients that were randomized; and all studies that were performed. Authors of SRs should choose one main outcome that matters to patients, and base their conclusions mainly on this outcome. Resistance as an outcome is a topic that should be addressed in all SRs of antibiotic treatment. Ethical aspects and especially patients' safety should be addressed in SRs. This article is protected by copyright. All rights reserved.
    Clinical Microbiology and Infection 12/2013; · 4.58 Impact Factor
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    Mical Paul, Leonard Leibovici
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    ABSTRACT: Systematic reviews attempt to answer a defined question or hypothesis through structured review of the evidence with a methodology that is pre-defined in a study protocol. Meta-analysis is merely the statistical method used to compile effect estimates from individual studies. Labelling studies as "meta-analysis" is a misnomer as would be labelling an observational study "multivariate" and the technical term "meta-analysis" is not to be confused with the study design "systematic review". Unfortunately, studies entitled "systematic reviews" do not always conform to the requisites of a systematic review and it is up to the reader to critically appraise the review and decide whether it indeed provides a systematic answer to the defined question. In this theme issue we hope to provide readers with some tools to critically appraise reviews using meta-analysis techniques. This article is protected by copyright. All rights reserved.
    Clinical Microbiology and Infection 12/2013; · 4.58 Impact Factor
  • M Paul
    Clinical Microbiology and Infection 11/2013; 19(11):991-992. · 4.58 Impact Factor
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    ABSTRACT: Immunosuppressed cancer patients are at increased risk of serious influenza-related complications. Guidelines, therefore, recommend influenza vaccination for these patients. However, data on vaccine effectiveness in this population is lacking, and the value of vaccination in this population remains unclear. To assess the effectiveness of influenza vaccine in immunosuppressed adults with malignancies. The primary review outcome is all-cause mortality, preferably at the end of the influenza season. Influenza-like illness (ILI, a clinical definition), confirmed influenza, pneumonia, any hospitalization and influenza-related mortality were defined as secondary outcomes. We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE and LILACS databases up to August 2013. We searched the following conference proceedings: ICAAC, ECCMID, IDSA (infectious disease conferences), ASH, ASBMT, EBMT (hematological), and ASCO (oncological) between the years 2006 to 2010. In addition, we scanned the references of all identified studies and pertinent reviews. We searched the websites of the manufacturers of influenza vaccine. Finally, we searched for ongoing or unpublished trials in clinical trial registry databases using the website. Randomized controlled trials (RCTs), prospective and retrospective cohort studies and case-control studies were considered, comparing inactivated influenza vaccines versus placebo, no vaccination or a different vaccine, in adults (16 years and over) with cancer. We considered solid malignancies treated with chemotherapy, haematological cancer patients treated or not treated with chemotherapy, cancer patients post-autologous (up to six months after transplantation) or allogeneic (at any time) hematopoietic stem cell transplantation. Two review authors independently assessed the risk of bias and extracted data from included studies adhering to Cochrane methodology. Meta-analysis could not be performed because of different outcome and denominator definitions in the included studies. We identified four studies: one RCT and three observational studies, including 2124 participants. One study reported results in person-years while the other three reported per person. The studies were performed between 1993 and 2012 and included adults with haematological diseases (two studies), patients following bone marrow transplantation (one study) and solid malignancies (three studies). Only two observational studies reported all-cause mortality; one showing an adjusted hazard ratio (HR) of 0.88 (95% CI 0.77 to 0.99) for death with vaccination and the other reporting an odds ratio (OR) of 0.43 (95% CI 0.26 to 0.71). The RCT reported a statistically significant reduction in ILI with vaccination, while no difference was observed in one observational study. Confirmed influenza rates were lower with vaccination in the three observational studies, the difference reaching statistical significance in one. Pneumonia was observed significantly less frequently with vaccination in one observational study, but no difference was detected in another or in the RCT. The RCT showed a reduction in hospitalizations following vaccination, while an observational study found no difference. No life-threatening or persistent adverse effects from vaccination were reported. The strength of evidence is limited by the low number of included studies and by their low methodological quality (high risk of bias). Observational data suggests a lower mortality with influenza vaccination. Infection-related outcomes were lower or similar with influenza vaccination. The strength of evidence is limited by the small number of studies and by the fact that only one was a RCT. Influenza vaccination is safe and the evidence, although weak, is in favour of vaccinating adults with cancer receiving chemotherapy.
    Cochrane database of systematic reviews (Online) 10/2013; 10:CD008983. · 5.70 Impact Factor
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    ABSTRACT: In the current theme issue, we have asked three expert teams to address the question of reliability of guidelines in the prevention and treatment of infectious diseases. Reliable guidelines should provide unbiased recommendations based on the best available evidence, allowing local application in different settings. Recommendations go a step further than a simple review of the evidence, as they may incorporate preferences, considerations of cost-effectiveness, applicability in special populations, temporal and local particularities. This article is protected by copyright. All rights reserved.
    Clinical Microbiology and Infection 10/2013; · 4.58 Impact Factor
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    ABSTRACT: Patients with cancer are at increased risk of developing complications of influenza. In this study, the authors assessed the effectiveness of influenza vaccination among cancer patients. A prospective, noninterventional cohort study was conducted during the 2010 to 2011 influenza season. The cohort included adult cancer patients with solid malignancies who were receiving chemotherapy and hematologic patients who had active disease. Patients who died between October and November 2010 (N = 43) were excluded. A comparison was made between patients who received the 2011 seasonal influenza vaccine with those who did not. The primary outcome was a composite of hospitalizations for fever or acute respiratory infections, pneumonia, and/or infection-related chemotherapy interruptions. All-cause mortality was a secondary outcome. A propensity-matched analysis was conducted based on the propensity for vaccination. Of 806 patients who were included, 387 (48%) were vaccinated. Factors that were associated independently with vaccination included past influenza vaccination, past pneumococcal vaccination, >6 months since cancer diagnosis, country of birth, and cancer type/status. The primary outcome occurred in 111 of 387 (28.7%) vaccinated patients versus 112 of 419 (26.7%) unvaccinated patients (P = .54). No association was observed between vaccination and the primary outcome in a propensity-matched analysis (N = 436) or during peak influenza activity. The mortality rate was 11.9% (46 of 387 patients) in vaccinated patients versus 19.1% (80 of 419 patients) in unvaccinated patients (P = .005). Vaccination retained a significant association with mortality on multivariable analysis (odds ratio, 2.31; 95% confidence interval, 1.4-3.79) and in a propensity-matched analysis (odds ratio, 2.39; 95% confidence interval, 1.32-4.32). Influenza vaccination was associated with lower mortality among cancer patients, although an association with infection-related complications could not be demonstrated. The current results support efforts to promote influenza vaccination in patients with cancer. Cancer 2013;. © 2013 American Cancer Society.
    Cancer 09/2013; · 5.20 Impact Factor
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    ABSTRACT: The aim of this study was to assess the value of surveillance cultures in identifying extended-spectrum beta-lactamase-producing Enterobacteriaceae (ESBL) carriers upon admission to hospital, and to identify risk factors for carriage. This prospective cross-sectional study included all hospital admissions over one week. Of 525 patients screened, 56 were positive for ESBLs. Half were only identified through screening. Four independent risk factors were identified: nursing home residency, hospitalization in the previous year, prior antibiotic treatment and prior ESBL carriage. Over 50% of the screened patients had at least one risk factor. By screening this targeted population, 87.5% of positive patients would have been identified.
    The Journal of hospital infection 09/2013; · 3.01 Impact Factor
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    ABSTRACT: To assess uniformity of criteria for hospitalization and management of inpatients with documented 2009 A/H1N1 influenza, at a time when national guidelines for management were issued by the public health authorities. This was a prospective observational cohort study. We included all adults with laboratory-confirmed pandemic 2009 A/H1N1 influenza in three hospitals in central Israel admitted between 22/7/2009 and 15/2/2010. We compared baseline data, results and treatment management between the three hospitals. Chi-square, ANOVA and Kruskal-WalLis tests were performed. Overall, 496 patients with documented 2009 A/H1N1 influenza were included; the mean age was 44 years (range 19-93). Of all the patients sampled, PCR for influenza was positive in 21.2% [178/840], 27.4% [124/453] and 18.6% [194/1043] in the three hospitals. Differences between hospitals in baseline patient characteristics were few. Significant differences were observed with regard to disease characteristics at admission, including temperature, respiratory symptoms, hypoxia, pulmonary infiltrates (33.7% [60/178], 19.4% [24/124] and 38.7% [75/194]), all influenza complications and severity of illness score (p < 0.05 for all). Differences were observed with regard to oseltamivir treatment, ranging from 79.5% to 98.9% of inpatients. Antibiotic treatment was common (overall 71%) but differences between hospitals were observed with regard to the antibiotic regimens used. The ratio of infectious disease physicians to hospital-bed ratio was low and variable (0.35, and 0.35 per 100 beds). There was significant variability between hospitals in the hospitalization and management of patients hospitalized with 2009 A/H1N1 influenza.
    Harefuah 09/2013; 152(9):524-8, 564.

Publication Stats

4k Citations
1,176.70 Total Impact Points

Institutions

  • 1997–2014
    • Tel Aviv University
      • • Faculty of Medicine
      • • Department of Internal Medicine
      • • Department of Family Medicine
      Tell Afif, Tel Aviv, Israel
  • 2013
    • Carmel Medical Center
      H̱efa, Haifa District, Israel
    • Aix-Marseille Université
      Marsiglia, Provence-Alpes-Côte d'Azur, France
    • Aalborg University Hospital
      • Department of Clinical Microbiology
      Aalborg, Region North Jutland, Denmark
  • 2012–2013
    • Rambam Medical Center
      H̱efa, Haifa District, Israel
  • 1970–2013
    • Rabin Medical Center
      • Department of Cardiology
      Tell Afif, Tel Aviv, Israel
  • 2011
    • Medical Research Council Unit, The Gambia Unit
      Bakau, Banjul, Gambia
  • 2004–2011
    • Meir Medical Center
      Kafr Saba, Central District, Israel
  • 2010
    • Johns Hopkins Medicine
      • Department of International Health
      Baltimore, MD, United States
  • 2009
    • Copenhagen University Hospital Hvidovre
      • Clinical Research Centre
      Hvidovre, Capital Region, Denmark
    • Ebonyi State University
      • Department of Paediatrics
      Abakaliki, Ebonyi State, Nigeria
  • 2007–2009
    • Aalborg University
      Ålborg, North Denmark, Denmark
  • 2006–2007
    • University of Bristol
      Bristol, England, United Kingdom