Varda Shalev

Tel Aviv University, Tell Afif, Tel Aviv, Israel

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Publications (105)372.69 Total impact

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    ABSTRACT: To assess the proportion of male versus female offspring of women diagnosed with SLE or RA, disorders in which female predominance is well known and PsA a disease in which female dominance is less established. The study population encompassed all females aged 16-46, who were members of the Maccabi Health Services (MHS) throughout the period of 2000-2011 and had at least one pregnancy. Data were retrieved from the computerized database of MHS, a 2-million enrollee health maintenance organization operating in Israel. The database was also used to collect data on patients with RA, SLE, and PsA. A total of 182,073 women had at least one indication of pregnancy during the study period. Among them, 546, 270, and 170 were diagnosed with RA, SLE, and PsA, respectively. The proportion of live-born males in 380,472 offspring of women free of these diseases was 51.5 % (95 % CI 51.4-51.7 %). The proportion (95 % CIs) of male offspring born to mothers diagnosed with of RA, SLE, and PsA were 46.3 % (42.3-50.3 %), 51.8 % (46.6-57.0 %), and 50.6 % (42.8-58.5 %), respectively. Our findings support the primary contribution of the hormonal phenotype rather than the genetic phenotype on autoimmunity. Neither patients with SLE or RA differ from the general population by the sex of their offspring.
    Annals of the Rheumatic Diseases 11/2014; · 9.27 Impact Factor
  • The Israel Medical Association journal: IMAJ 10/2014; 16(10):625-6. · 0.90 Impact Factor
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    ABSTRACT: The incidence of skin cancer, both melanoma and keratinocyte cancers (KC) is rising throughout the world, specifically squamous cell carcinomas(SCC) and basal cell carcinoma(BCC), being the most common of all cancers.
    British Journal of Dermatology 06/2014; 172(1). · 3.76 Impact Factor
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    ABSTRACT: Previous assessments of the prevalence of resistant hypertension (RH) in uncontrolled blood pressure (BP) have ranged from 3% to 30%. Using real-world data, our aim was to estimate the prevalence of RH in patients belonging to the Maccabi Healthcare Services, a 2-million-member health organization in Israel. From 2010 to 2011, all hypertensive patients with ≥2 recorded BP measurements during a minimum period of 6 months were identified. Patients were considered uncontrolled if their most recent BP during the study period and their mean systolic BP or diastolic BP during a preceding period of ≥6months were systolic BP ≥140 mm Hg or diastolic BP ≥90 mm Hg, or systolic BP ≥130 mm Hg or diastolic BP ≥80 mm Hg in chronic kidney disease or diabetes mellitus. Uncontrolled patients taking diuretics and ≥2 antihypertensive therapy classes at their maximal recommended dose were regarded as resistant hypertensives. A total of 172 432 patients were eligible for the study. Uncontrolled BP was found in 35.9% (n=65 710). Overall, 2.2% of the uncontrolled patients (n=1487) were resistant hypertensives. Patients with RH were characterized by a significantly (P<0.01) older age, higher body mass index, and multicomorbidity (including dyslipidemia, diabetes mellitus, and impaired renal function) compared with patients with controlled hypertension receiving equivalent treatment. The results of this large population-based study indicate a substantially lower prevalence of RH than previously reported. Most patients with uncontrolled BP took less than the maximal recommended antihypertensive treatment.
    Hypertension 06/2014; · 7.63 Impact Factor
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    ABSTRACT: Background: The dramatic increase in autism spectrum disorder (ASD) prevalence has been attributed to the broadening of diagnostic criteria, greater awareness, improved case finding methods, and the development of services for children with ASD. Diagnostic substitution has also been suggested as a reason for this increase, with several studies pointing to an increase in the diagnosis of ASD and a decrease in the diagnoses of intellectual disabilities, and other language and developmental disorders. However, to our knowledge, no studies have examined whether shifts in psychiatric diagnoses could contribute to the rise in ASD prevalence. Objectives: To describe the changes in diagnoses of autism and mental health disorders in children in Israel between 2003 and 2012, using data from psychiatrists in Maccabi Healthcare Services (MHS), a large healthcare organization in Israel. Methods: A search of the MHS computerized databases was conducted for all diagnoses given to children (up to the age of 18) by psychiatrists from 2003 to 2012. Diagnoses were grouped by year and divided into ten broad categories, such as ASD, anxiety, and phobia. If a child received a diagnosis that fell into multiple categories, the diagnosis was listed in all relevant categories. However, if a child received the same type of diagnosis twice or more in a single year, the diagnosis was listed only once. The relative percentage change was calculated and chi square analysis was performed. Results: The total number of children diagnosed by psychiatrists in MHS increased from 1499 children in 2003 to 7327 in 2012. ASD accounted for 6.1% of all diagnoses in 2003, compared to 10.4% in 2012, representing a relative percentage increase of 69.2% (p<0.001). Statistically significant (p<0.01) relative increases between 2003 and 2012 were also found for behavior problems (60.7%), anxiety (58.6%) and ADHD (38.4%). A significant (p<0.001) decrease in the relative percentage between the same years was found for psychosis (58.5%), schizophrenia (40.8%) and depression (35.4%). Non-significant changes were found for phobia, obsessive compulsive disorder and bipolar diagnoses. Conclusions: Results indicate a substantial shift in psychiatric case mix among children (up to the age of 18) between 2003 and 2012 in one of Israel’s largest healthcare organizations. ASD accounts for a growing proportion of all cases diagnosed by psychiatrists. While there was a relative increase also in behavior problems, anxiety and ADHD, there was a relative decrease in psychosis, schizophrenia, and depression. This shift may reflect psychiatric diagnosis substitution over time with an increasing number of children receiving an ASD diagnosis instead of other psychiatric diagnoses. Possible explanations for the shift in psychiatric case mix include increased awareness as well as a significant increase in services provided to children and adolescents with ASD.
    2014 International Meeting for Autism Research; 05/2014
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    ABSTRACT: To investigate the prevalence and incidence of glaucoma in a large health maintenance organization (HMO) in Israel. A population-based retrospective cohort study, conducted using electronic medical database. Collected data included personal and medical characteristics. Maccabi Healthcare Services, the second largest HMO in Israel insuring 2 million members and serving 25% of the population with a nationwide distribution. Maccabi members from January 2003 to December 2010. Prevalence and incidence of glaucoma according to the International Classification of Diseases, 9th revision, Clinical Modification diagnostic codes. A total of 15,708 prevalent glaucoma patients were identified among active members of Maccabi in December 2010. A total of 15,332(97.6%) were 40 years or older, with a point prevalence of 2.2%. Prevalence of glaucoma was strongly associated with age, ranging from 0.28%at age 40-50 to 9.2% among elderly aged 80 or above. The 5 most prevalent diagnoses were open angle glaucoma (1.61%), exfoliation glaucoma (0.20%), unspecified glaucoma (0.17%), angle closure (0.11%), and normal tension glaucoma (0.06%). We identified 6,674 incident glaucoma patients diagnosed between 2003 and 2010. The observed incidence density rate among 40+ year old members was 1.84 (1.79-1.88) new cases per 1000 person years. Median age at diagnosis was 64 years old. The risk of glaucoma was similar between sexes up to age 70 years, and was significantly (P<0.01) higher in men in older ages. Glaucoma affects nearly 10% of the elderly population in Maccabi with the highest risk of diagnoses at age 70 to 74. Since glaucoma leads to irreversible vision loss, the present estimates of morbidity should be of significant concern.
    American Journal of Ophthalmology 05/2014; · 4.02 Impact Factor
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    ABSTRACT: Background/Aims: A worldwide decline in the age at menarche (AAM) has been reported in recent decades. This trend has been also clinically observed among Israeli women and was reported in our previous study. Methods: We reviewed the literature reporting the mean AAM in Israel during the past century. Studies were excluded if participants had been investigated due to illness or any condition which could affect sexual maturation. Mean AAM was analyzed using a simple linear regression weighted for number of participants in each birth cohort and stratified to birth cohorts before and after 1970, based on the outcome of our previous study. Results: AAM varied little among women born between 1875 and 1970, but there was a clear downwards trend from 13.4 in 1970 to 12.8 two decades later. In a stratified analysis we found a significant negative association between birth year and AAM in the birth cohort after 1970 (standardized β coefficient = -0.94 per year, R(2) = 0.87; p < 0.001). Conclusion: These results suggest a significant decline in mean AAM in Israeli women born in 1970 or later. © 2014 S. Karger AG, Basel.
    Hormone Research in Paediatrics 02/2014; · 1.55 Impact Factor
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    ABSTRACT: The aim of this population-based study is to describe trends in the characteristics and treatment patterns of statin initiators over the first decade of the 21st century. New statin use was studied retrospectively using the database of Maccabi Healthcare Services (MHS), a large Israeli health maintenance organization. Statin initiators were defined as MHS members aged ≥30 years who first purchased statins between 2000 and 2010. The starting dose was calculated in simvastatin equivalents based on the World Health Organization's daily defined dose index. Persistence was calculated as the percentage of days covered (PDC) with statins during the first year of therapy. Statin initiation peaked in 2005 and decreased from 38.6 to 18.6 per 1,000 in the period 2005-2010. The average age at therapy initiation decreased from 58.9 (±12.0) to 54.5 (±11.7) years, and the average (SD) baseline low-density lipoprotein cholesterol (LDL-C) decreased from 4.2 (±1.1) to 4.0 (±0.9) mmol/l during the study period. Women were on average 3 years older than men at treatment initiation, with a higher baseline LDL-C. Among statin initiators, the prevalence of ischemic heart disease (IHD) decreased from 17.8 to 6.7 %, and diabetes prevalence increased from 8.6 to 15.7 %, peaking in 2008 (18.0 %). The PDC with statins ranged between 52.9 and 57.7 %. Simvastatin use at initiation increased from 27.5 % in 2000 to >90 % since 2002. Starting dose increased from 18.5 (±8.9) to 24.3 (±13.7) mg simvastatin equivalent. Among the study population, statin initiators were increasingly characterized by a lower cardiovascular risk-namely, younger individuals without IHD and with a lower baseline LDL-C. These trends underscore the important shift towards statin initiation for primary prevention, as well as the need to balance between benefits and the potential side effect of statins.
    European Journal of Clinical Pharmacology 01/2014; · 2.70 Impact Factor
  • Epidemiology (Cambridge, Mass.) 01/2014; 25(1):152-3. · 6.18 Impact Factor
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    ABSTRACT: Red blood cell distribution width (RDW) has been shown to predict cardiovascular mortality in various populations, but studies were less conclusive regarding cardiovascular morbidity. We aimed at evaluating the prognostic effect of RDW on cardiovascular morbidity and all-cause mortality in the largest community cohort to date.We utilised the computerised database of a large community based healthcare maintenance organization (HMO) in Israel to identify a cohort of 225,006 eligible patients aged 40 or above who performed a blood count during 2006. We evaluated the relationship between 1% increments of RDW values and major cardiovascular events and all-cause mortality over a period of five years. A total of 21,939 incident cases of a major cardiovascular event and 4,287 deaths were documented during a total of six years of follow up, respectively. In comparison with patients with RDW level <13%, the hazard ratio for total mortality gradually increased to 4.57 (95% confidence interval [CI]: 3.35-6.24, p<0.001) among male patients and to 3.26 (95% CI: 2.49-4.28, p<0.001) among female patients with a RDW of 17% or above. Similar results were evident in anaemic and non-anaemic populations. RDW above 17% was also associated with a modest increased risk of major cardiovascular events in females 1.26 (95% CI: 1.03-1.52, p=0.021), while in men it was not significant, 1.08 (95% CI: 0.82-1.41, p=NS). In conclusion, increasing RDW levels significantly increased risk of cardiovascular morbidity and all-cause mortality. Our observation is evident in both anaemic and non-anaemic patients.
    Thrombosis and Haemostasis 10/2013; 111(2). · 5.76 Impact Factor
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    ABSTRACT: Anemia on admission and during hospitalization is associated with poor short and long term prognosis among patients with acute coronary syndrome (ACS). Our objective was to examine the prognostic implications of longitudinal hemoglobin (Hb) levels following a first acute myocardial infarction (AMI). We utilized data obtained from the computerized database of a large community based health care maintenance organization to identify patients who survived for at least 6months following a first AMI, during the years 2003-2010. Hazard ratios were calculated using Cox proportional regression models with various Hb measurements as dependent variables, and net reclassification improvement (NRI) was applied to evaluate the prognostic usefulness of these Hb measurements. Last Hb measurement during a 6-24month follow-up period was found to have the highest prognostic power. In males, Hb levels below 13g/dL were gradually associated with a higher risk of events, reaching a HR of 4.13 at Hb levels <11g/dL. In females, only Hb levels lower than 11g/dL were significantly associated with a higher event rate (HR=2.42, p=0.003). Hb decrease was significantly associated with an increased risk in both genders, even among non-anemic patients at baseline. Anemia and Hb decrement following a first AMI are associated with worse prognosis and elevated risk of combined all cause mortality and recurrent cardiac events.
    International journal of cardiology 10/2013; · 6.18 Impact Factor
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    ABSTRACT: To assess the incidence of Herpes Zoster (HZ) and its complications in the Israeli general population and specifically in immune-compromised individuals, and to identify risk factors for developing HZ and post-herpetic neuralgia (PHN). A retrospective database search for newly diagnosed cases of HZ and of PHN during 2006-2010 was conducted using the comprehensive longitudinal database of Maccabi Health Services. Cox proportional hazards models were used to assess associations between risk factors and HZ and PHN. During 2006-2010 there were 28,977 newly diagnosed cases of HZ and 1,508 newly diagnosed cases of PHN. Incidence density rate of HZ was 3.46 per 1,000 person-years in the total population and 12.8 per 1,000 person-years in immune-compromised patients. HZ and PHN incidence increased sharply with age. 12.4% and 3.1% of elderly HZ patients (≥65 years) developed PHN or ophthalmic complications, respectively. In multivariable analyses, HZ and PHN were associated with female sex, higher socio-economic status, diabetes mellitus, cancer history, and HIV treatment. Extrapolating to the entire Israeli population, we estimate over 24,000 new cases of HZ and 1,250 new cases of PHN each year. Cost-effectiveness analysis should be performed to determine the threshold age for vaccination against HZ.
    The Journal of infection 07/2013; · 4.13 Impact Factor
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    ABSTRACT: To validate the use of drug dispensing data as a measure of drug exposure and to quantify the association between persistence with statin therapy and low-density lipoprotein cholesterol (LDL) levels using real-life community data. Retrospective, population-based cohort study. Maccabi Healthcare Services (MHS) database, which contains linked prescription drug information, hospitalization records, and laboratory test results of 2 million members of the second largest health organization in Israel. A total of 87,219 primary prevention patients and 15,139 secondary prevention patients who were MHS members and who started statin therapy between 1998 and 2008. Baseline and follow-up LDL levels were documented from 3 months before the date of first dispensed statin (index date) to 6 months afterward. Persistence was assessed by proportion of days covered (PDC) with statins during the follow-up period. Over the follow-up period, significant (p<0.001) reductions in LDL levels of 54, 33, and 13 mg/dl were noted among highly persistent (PDC ≥ 80%), moderately persistent (34% ≤ PDC < 79%), and poorly persistent statins users (PDC ≤ 33%), respectively. The reduction was observed as early as 2-3 weeks after therapy initiation. In a multivariable model controlling for baseline LDL level and traditional coronary heart disease risk factors (diabetes mellitus, hypertension), high persistence with statin therapy was associated with a 27% and 25% decrement in LDL level among the primary and secondary prevention cohorts, respectively. Similarly, a higher proportion of the persistent statins users reached their target LDL level within the study follow-up period: 80% and 58% among primary and secondary prevention cohorts, respectively, compared with only 28% and 17%, respectively, among poorly persistent patients. In this observational population-based study, calculated PDC with statins during study follow-up was strongly associated with drug effect of LDL level reduction. The results agree with previous estimates of statin efficacy from randomized clinical trials, supporting the validity of using PDC methods as a measure of drug exposure.
    Pharmacotherapy 07/2013; · 2.31 Impact Factor
  • Value in Health 05/2013; 16(3):A176. · 2.89 Impact Factor
  • Value in Health 05/2013; 16(3):A199. · 2.89 Impact Factor
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    ABSTRACT: Infection might be associated with increased risk of venous thromboembolism (VTE) and arterial thrombosis. Specific hypotheses have been raised regarding the procoagulant response induced by acute cytomegalovirus (CMV) infection. Accordingly, we investigated the 6-month incidence of VTE and/or arterial thrombosis in patients that had been tested positive for CMV-IgM antibodies in a large health maintenance organization. Logistic regression analysis was used to identify independent risk factors for VTE and arterial thrombosis. Among 90,515 patients eligible for the VTE analysis and 90,805 patients eligible for the arterial thrombosis analysis, 6,205 (6.9 %) and 6,222 (6.9 %) patients were tested positive for CMV-IgM antibodies, respectively. During 6 months of follow-up from index date, the incidence rates per 1,000 capita of VTE among CMV-IgM seropositive and CMV-IgM seronegative patients were 3.06 (19 patients) and 1.36 (115 patients), respectively (odds ratio (OR) 2.25; 95 % confidence intervals (95 % CI) 1.38-3.66; p = 0.003). CMV-IgM seropositivity was independently associated with VTE appearance (OR 2.49; 95 % CI 1.53-4.06; p < 0.0001) following adjustment for age, sex, and other confounders. The incidence rates per 1,000 capita of arterial thrombosis among CMV-IgM seropositive and CMV-IgM seronegative patients were 1.12 (7 patients) and 1.06 (90 patients), respectively (OR 1.06; 95 % CI 0.49-2.28; p = 0.840). CMV-IgM seropositivity was not associated with arterial thrombosis. We conclude that acute CMV infection might be associated with an increased short-term VTE risk. To the best of our knowledge, this is the largest study ever to confirm this association.
    Annals of Hematology 03/2013; 92(7). · 2.40 Impact Factor
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    ABSTRACT: Objective. To assess the adherence and persistence with allopurinol therapy among gout patients and to identify risk factors for therapy discontinuation.Methods. The study population included adults in Maccabi Healthcare Services, a 2-million member health maintenance organization in Israel, who were diagnosed with gout between 2002 and 2008. Adherence with allopurinol was retrospectively assessed by calculating the proportion of days covered of dispensed prescriptions. Persistence was assessed by calculating the mean proportion of follow-up days covered with allopurinol for every study participant.Results. A total of 7644 patients were identified. Among men, the incidence of gout was strongly associated with age, ranging from 0.5 per 1000 among adults younger than 45 years to more than 36 per 1000 among elderly men aged 85 or older). A total of 1331 gout patients (17% of the study population) were adherent to allopurinol therapy, 36% and 47% had partial and poor adherence, respectively. Persistence analysis indicated that the average duration until therapy was discontinued was similar among men (358 days) and women (379 days). Women aged 45-64 years, non-married individuals, those of low socioeconomic status and those with lower body weight were more likely to discontinue therapy. Logistic regression (n = 2471, 32% of the study sample) showed a 4.5 risk of non-compliance among 45- to 65-year-old women. Better compliance was achieved among those with comorbidities, particularly among patients with concomitant cardiovascular disease.Conclusion. Only one out of six gout patients is adherent with allopurinol. Intervention programmes to increase adherence with treatment should focus on high-risk populations.
    Rheumatology (Oxford, England) 02/2013; · 4.44 Impact Factor
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    ABSTRACT: OBJECTIVE: To assess long-term cancer risks associated with in vitro fertilization (IVF). DESIGN: Record-linkage study. SETTING: Health maintenance organization in Israel. PATIENT(S): A total of 87,403 women evaluated and/or treated for infertility on or after September 25, 1994, who were followed for cancer development through June 22, 2011: 522 breast, 41 endometrial, 45 ovarian, 311 in situ cervical, and 32 invasive cervical cancers were identified. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Hazard ratios (HRs) for specific cancers. RESULT(S): We found no significant relationships of IVF exposures to the risks of breast, endometrial, or ovarian cancers. However, compared with women with no fertility treatment, the HR for ovarian cancer associated with IVF was 1.58 (95% confidence interval [CI] 0.75-3.29), with higher risk among those receiving four or more cycles (HR 1.78, 95% CI 0.76-4.13). There was also a nonsignificantly elevated risk for endometrial cancer among women who received 1-3 IVF cycles (HR 1.94, 95% CI 0.73-5.12), but additional cycles were associated with less risk. In contrast, the risk of in situ cervical cancer was significantly reduced and invasive cervical cancer nonsignificantly reduced among women receiving IVF as well as other fertility treatments. CONCLUSION(S): Our results regarding long-term effects were largely reassuring, but women receiving IVF should continue to be monitored given that the procedures involve potent ovulation stimulators and repeated ovarian punctures.
    Fertility and sterility 01/2013; · 4.30 Impact Factor
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    ABSTRACT: While Israel is by far number one in the world of in-vitro fertilization (IVF) treatments per capita, detailed information about the outcome of these treatments is not available. To describe IVF activity during the years 2007-2010 in Maccabi Healthcare Services, an independent health provider that reimburses IVF treatments. Data on IVF cycles and live births were collected from the Maccabi Healthcare Services infertility registry and analyzed by year and age at cycle start. During the four years surveyed, the average patients' age rose from 35.12 to 36.19 years. The number of IVF treatments increased by 50%, while the "live birth" rate fell from 18.8% in 2007, to 14.8% in 2010. A drop in success rate was noted in patients >35 years of age, and more so in patients >40 years of age. Beyond 43 years of age, the success rate was in the low one digit range. The estimated cost of a single live birth in this age group is NIS 399,000. The clinical results are not encouraging relative to IVF outcomes in Europe and the U.S.A. SurprisingLy, and contrary to worldwide trends, the success rate in Israel decreased during the surveyed years. We speculate that the main reason is that many IVF treatments are conducted in patients that a priori have a very low chance of success. A nationwide prospective IVF registry should be implemented.
    Harefuah 01/2013; 152(1):11-5, 60.
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    ABSTRACT: OBJECTIVE: To investigate whether treatment initiated with an angiotensin-converting enzyme inhibitor (ACE-I) or an angiotensin II receptor blocker (ARB) for patients with ischemic heart disease, hypertension, or diabetes causes a reduction in hemoglobin (Hb) levels. PATIENTS AND METHODS: This was a retrospective cohort analysis using the computerized database of a large health maintenance organization. Included were all adults with a first purchase of an ACE-I, an ARB, or a calcium channel blocker (CCB) between January 1, 2004, and December 31, 2009, defined as the index date. Measures of Hb levels before and 1 year after the index date were reviewed, and the change was calculated. All the analyses were stratified by pharmaceutical class. The main exposure variables were the proportion of days covered (PDC) by these drugs and the mean enalapril dosage (for enalapril users only). RESULTS: Levels of Hb before and after treatment were available for 14,754 patients taking ACE-Is, 751 taking ARBs, and 3087 taking CCBs. A high PDC was significantly associated with greater yearly reductions in Hb levels compared with a low PDC for CCB use, but was more pronounced for ACE-I and ARB use. A high PDC was also associated with a higher odds of developing anemia in ACE-I users (odds ratio [OR], 1.59; P<.001) and ARB users (OR, 2.21; P=.05). In nonanemic enalapril users, every 10-mg increment in daily dose was associated with an OR of 1.45 for the development of anemia (P<.001). The association remained after excluding nonadherent patients. CONCLUSION: Levels of Hb are reduced during the first year of use of ACE-Is and to a lesser extent with use of ARBs. This association is dose dependent and is not explained by patient adherence.
    Mayo Clinic Proceedings 11/2012; · 5.79 Impact Factor

Publication Stats

928 Citations
372.69 Total Impact Points


  • 2003–2014
    • Tel Aviv University
      • • Department of Internal Medicine
      • • Faculty of Medicine
      Tell Afif, Tel Aviv, Israel
  • 2012–2013
    • Tel Aviv Sourasky Medical Center
      • Department of Ophthalmology
      Tell Afif, Tel Aviv, Israel
  • 2008–2011
    • Meir Medical Center
      Kafr Saba, Central District, Israel
  • 2010
    • Hadassah Medical Center
      Yerushalayim, Jerusalem District, Israel