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Non-adherence with bisphosphonates among patients with osteoporosis: impact on fracture risk and healthcare cost‏.

Chodick G, Moser SS, Goldshtein I
Expert Rev Pharmacoecon Outcomes Res
ABSTRACT
Related Articles
Non-adherence with bisphosphonates among patients with osteoporosis: impact on fracture risk and healthcare cost‏.
Expert Rev Pharmacoecon Outcomes Res. 2016 Jun;16(3):359-70
Authors: Chodick G, Moser SS, Goldshtein I
Abstract
Osteoporosis-related fractures at the spine and hip have a substantial impact on mortality, morbidity, and quality of life in older adults worldwide. Adherence to bisphosphonates is essential for effective treatment and fracture prevention. Nevertheless, numerous studies from various populations and study designs clearly indicated that adherence and persistence are poor with more than 50% of patients discontinuing therapy within one year. This is primarily explained by mild adverse effects, dosing regimens, and costs. Studies have also shown that good adherence is associated with reduced osteoporosis-related and non-related healthcare costs as soon as 2 years from therapy initiation. Nonetheless, we found only little improvement in adherence rates over the years. In light of the importance of medication adherence and the limited success of previous programs, other than reducing dosing frequency, new directions should be explored to engage patients and care givers in order to improve adherence and prevent fractures.
PMID: 27015247 [PubMed - in process]
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Influenza vaccination: reduction in hospitalizations and death rates among members of "Maccabi Healthcare Services" during the 2000-2001 influenza season.

Shapiro Y, Shemer J, Heymann A, Shalev V, Maharshak N, Chodik G, Green MS, Kokia E
Isr Med Assoc J
ABSTRACT
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Influenza vaccination: reduction in hospitalizations and death rates among members of "Maccabi Healthcare Services" during the 2000-2001 influenza season.
Isr Med Assoc J. 2003 Oct;5(10):706-8
Authors: Shapiro Y, Shemer J, Heymann A, Shalev V, Maharshak N, Chodik G, Green MS, Kokia E
Abstract
BACKGROUND: Upper respiratory tract illnesses have been associated with an increased risk of morbidity and mortality.
OBJECTIVE: To assess the influence of vaccination against influenza on the risk of hospitalization in internal medicine and geriatric wards, and the risk of death from all causes during the 2000-2001 influenza season.
METHODS: A historical cohort study was conducted using computerized general practitioner records on patients aged 65 years and above, members of "Maccabi Healthcare Services"--the second largest health maintenance organization in Israel with 1.6 million members. The patients were divided into high and low risk groups corresponding to coexisting conditions, and were studied. Administrative and clinical data were used to evaluate outcomes.
RESULTS: Of the 84,613 subjects in the cohort 42.8% were immunized. At baseline, vaccinated subjects were sicker and had higher rates of coexisting conditions than unvaccinated subjects. Vaccination against influenza was associated with a 30% reduction in hospitalization rates and 70% in mortality rates in the high risk group. The NNT (number needed to treat) measured to prevent one hospitalization was 53.2 (28.2 in the high risk group and 100.4 in the low risk group). When referring to length of hospitalization, one vaccine was needed to prevent 1 day of hospitalization among the high risk group. Analyses according to age and the presence or absence of major medical conditions at baseline revealed similar findings across all subgroups.
CONCLUSIONS: In the elderly, vaccination against influenza is associated with a reduction in both the total risk of hospitalization and in the risk of death from all causes during the influenza season. These findings compel the rationale to increase compliance with recommendations for annual influenza vaccination among the elderly.
PMID: 14719464 [PubMed - indexed for MEDLINE]
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Development and validation of a predictive model for detection of colorectal cancer in primary care by analysis of complete blood counts: a binational retrospective study.

Kinar Y, Kalkstein N, Akiva P, Levin B, Half EE, Goldshtein I, Chodick G, Shalev V
J Am Med Inform Assoc
ABSTRACT
Related Articles
Development and validation of a predictive model for detection of colorectal cancer in primary care by analysis of complete blood counts: a binational retrospective study.
J Am Med Inform Assoc. 2016 Feb 15;
Authors: Kinar Y, Kalkstein N, Akiva P, Levin B, Half EE, Goldshtein I, Chodick G, Shalev V
Abstract
OBJECTIVE: The use of risk prediction models grows as electronic medical records become widely available. Here, we develop and validate a model to identify individuals at increased risk for colorectal cancer (CRC) by analyzing blood counts, age, and sex, then determine the model's value when used to supplement conventional screening.
MATERIALS AND METHODS: Primary care data were collected from a cohort of 606 403 Israelis (of whom 3135 were diagnosed with CRC) and a case control UK dataset of 5061 CRC cases and 25 613 controls. The model was developed on 80% of the Israeli dataset and validated using the remaining Israeli and UK datasets. Performance was evaluated according to the area under the curve, specificity, and odds ratio at several working points.
RESULTS: Using blood counts obtained 3-6 months before diagnosis, the area under the curve for detecting CRC was 0.82 ± 0.01 for the Israeli validation set. The specificity was 88 ± 2% in the Israeli validation set and 94 ± 1% in the UK dataset. Detecting 50% of CRC cases, the odds ratio was 26 ± 5 and 40 ± 6, respectively, for a false-positive rate of 0.5%. Specificity for 50% detection was 87 ± 2% a year before diagnosis and 85 ± 2% for localized cancers. When used in addition to the fecal occult blood test, our model enabled more than a 2-fold increase in CRC detection.
DISCUSSION: Comparable results in 2 unrelated populations suggest that the model should generally apply to the detection of CRC in other groups. The model's performance is superior to current iron deficiency anemia management guidelines, and may help physicians to identify individuals requiring additional clinical evaluation.
CONCLUSIONS: Our model may help to detect CRC earlier in clinical practice.
PMID: 26911814 [PubMed - as supplied by publisher]
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The Maccabi Glaucoma Study: Treatment Patterns and Persistence With Glaucoma Therapy in a Large Israeli Health Maintenance Organization.

Goldshtein I, Shalev V, Zigman N, Chodick G, Levkovitch-Verbin H
J Glaucoma
ABSTRACT
Related Articles
The Maccabi Glaucoma Study: Treatment Patterns and Persistence With Glaucoma Therapy in a Large Israeli Health Maintenance Organization.
J Glaucoma. 2016 Apr;25(4):e386-91
Authors: Goldshtein I, Shalev V, Zigman N, Chodick G, Levkovitch-Verbin H
Abstract
PURPOSE: To describe treatment patterns, adherence, and persistence with initial therapy among glaucoma patients in the community.
MATERIALS AND METHODS: A population-based historical prospective cohort study, using the electronic medical databases of Maccabi Healthcare Services, a 2 million member health maintenance organization in Israel. Newly diagnosed glaucoma patients between 2003 and 2010, who purchased at least 1 antiglaucoma medication, were followed up to December 31, 2012. Outcome measures included medication adherence analyzed by proportion of days covered by drugs during follow-up time, and persistence with initial therapy measured by time until switch or discontinuation of first-line therapy.
RESULTS: A total of 5934 incident definite glaucoma patients were identified, 13% of whom were nonadherent with therapy (covered <20% of the follow-up time), and only 25% exhibited high adherence (covered at least 80% of the follow-up period). Adherence was positively associated with female sex, age, socioeconomic status, frequent follow-up visits, and higher baseline intraocular pressure. Lower median adherence (P<0.01) was observed among patients of normal tension glaucoma (52%) and angle closure (59%) as compared with open angle (65%) and exfoliation glaucoma (68%). Patients treated by glaucoma specialists had similar adherence to those treated by general ophthalmologists (proportion of days covered=65% vs. 63%, P=0.42). Persistence with initial line of therapy varied by type of medication, with prostaglandin initiators exhibiting the highest persistence (13% reduced likelihood of switch or discontinuation as compared with β-blockers, P<0.01) and α-agonists the lowest persistence (39% increased likelihood of switch or discontinuation as compared with β-blockers, P<0.01).
CONCLUSIONS: This large-scale analysis of real-world use of glaucoma medications reveals that adherence to glaucoma therapy is associated with medication type, patient's sex, age, socioeconomic status, type of glaucoma, follow-up visits, and baseline intraocular pressure.
PMID: 26900826 [PubMed - in process]
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Cost and Consequences of Nonadherence With Oral Bisphosphonate Therapy: Findings From a Real-World Data Analysis.

Sharman Moser S, Yu J, Goldshtein I, Ish-Shalom S, Rouach V, Shalev V, Modi A, Chodick G
Ann Pharmacother
ABSTRACT
Related Articles
Cost and Consequences of Nonadherence With Oral Bisphosphonate Therapy: Findings From a Real-World Data Analysis.
Ann Pharmacother. 2016 Apr;50(4):262-9
Authors: Sharman Moser S, Yu J, Goldshtein I, Ish-Shalom S, Rouach V, Shalev V, Modi A, Chodick G
Abstract
BACKGROUND: Adherence to osteoporosis treatment remains poor despite available treatments and physician and patient education. This study aims to determine the effect of low adherence in real-world data.
OBJECTIVE: To examine the association between adherence with oral bisphosphonate therapy and fracture risk as well as health care resource utilization.
METHODS: Women included in this retrospective analysis were 55 years or older and had started oral bisphosphonate therapy between 2005 and 2011 in a large not-for-profit health care center in Israel. Adherence to therapy was measured by the medication possession ratio (MPR) during the first year from therapy initiation. Patients with MPR lower than 70% were considered nonadherent. Study outcomes were osteoporotic fracture events and health care utilization (including physician visits and hospitalizations) during the second year from therapy initiation.
RESULTS: Among the 17 770 women included in the analysis (mean age = 66.5 years; SD = ±8.3 years), 48.9% were nonadherent to therapy during the first year of treatment. Osteoporotic fracture risks during the second year among adherent and nonadherent patients were 2.1% and 2.5%, respectively (P = 0.1). When analysis was limited to patients 75 years or older, nonadherence with bisphosphonates was associated with an adjusted odds ratio of 1.49 (95% CI = 1.08-2.04) for osteoporotic fractures compared with adherent patients. Nonadherent patients had 13.4% higher medical costs than their adherent counterparts among patients 75 years and older (P = 0.002).
CONCLUSIONS: In patients 75 years and older, nonadherence with oral bisphosphonates can be associated with significantly greater short-term risk of osteoporotic fractures and higher utilization of health care services.
PMID: 26783359 [PubMed - in process]
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Kidney-Failure Risk Projection for the Living Kidney-Donor Candidate.

Grams ME, Sang Y, Levey AS, Matsushita K, Ballew S, Chang AR, Chow EK, Kasiske BL, Kovesdy CP, Nadkarni GN, Shalev V, Segev DL, Coresh J, Lentine KL, Garg AX, Chronic Kidney Disease Prognosis Consortium
N Engl J Med
ABSTRACT
Related Articles
Kidney-Failure Risk Projection for the Living Kidney-Donor Candidate.
N Engl J Med. 2016 Feb 4;374(5):411-21
Authors: Grams ME, Sang Y, Levey AS, Matsushita K, Ballew S, Chang AR, Chow EK, Kasiske BL, Kovesdy CP, Nadkarni GN, Shalev V, Segev DL, Coresh J, Lentine KL, Garg AX, Chronic Kidney Disease Prognosis Consortium
Abstract
BACKGROUND: Evaluation of candidates to serve as living kidney donors relies on screening for individual risk factors for end-stage renal disease (ESRD). To support an empirical approach to donor selection, we developed a tool that simultaneously incorporates multiple health characteristics to estimate a person's probable long-term risk of ESRD if that person does not donate a kidney.
METHODS: We used risk associations from a meta-analysis of seven general population cohorts, calibrated to the population-level incidence of ESRD and mortality in the United States, to project the estimated long-term incidence of ESRD among persons who do not donate a kidney, according to 10 demographic and health characteristics. We then compared 15-year projections with the observed risk among 52,998 living kidney donors in the United States.
RESULTS: A total of 4,933,314 participants from seven cohorts were followed for a median of 4 to 16 years. For a 40-year-old person with health characteristics that were similar to those of age-matched kidney donors, the 15-year projections of the risk of ESRD in the absence of donation varied according to race and sex; the risk was 0.24% among black men, 0.15% among black women, 0.06% among white men, and 0.04% among white women. Risk projections were higher in the presence of a lower estimated glomerular filtration rate, higher albuminuria, hypertension, current or former smoking, diabetes, and obesity. In the model-based lifetime projections, the risk of ESRD was highest among persons in the youngest age group, particularly among young blacks. The 15-year observed risks after donation among kidney donors in the United States were 3.5 to 5.3 times as high as the projected risks in the absence of donation.
CONCLUSIONS: Multiple demographic and health characteristics may be used together to estimate the projected long-term risk of ESRD among living kidney-donor candidates and to inform acceptance criteria for kidney donors. (Funded by the National Institute of Diabetes and Digestive and Kidney Diseases and others.).
PMID: 26544982 [PubMed - indexed for MEDLINE]
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Epidemiology of hepatitis C virus infection in a large Israeli health maintenance organization.

Weil C, Nwankwo C, Friedman M, Kenet G, Chodick G, Shalev V
J Med Virol
ABSTRACT
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Epidemiology of hepatitis C virus infection in a large Israeli health maintenance organization.
J Med Virol. 2016 Jun;88(6):1044-50
Authors: Weil C, Nwankwo C, Friedman M, Kenet G, Chodick G, Shalev V
Abstract
Hepatitis C affects an estimated 130 million people worldwide and is a major cause of chronic liver disease. This retrospective database study aims to describe the epidemiology of HCV-infected patients in Maccabi Healthcare Services, a 2-million-member health maintenance organization in Israel. HCV was identified by cross-linking diagnoses, laboratory data, and dispensed HCV treatment (1993-2013). The point-prevalence of HCV in 2012 and annual incidence of newly-diagnosed HCV during 2003-2012 (index period) were calculated. The age-adjusted prevalence of HCV was 5.19/1,000 population (n = 10,648). The highest prevalence was found among males and in patients aged 35-54 years. Two thirds of HCV-infected patients were immigrants from the former Soviet Union (FSU). HCV genotype 1 was predominant (67%). A total of 6,150 patients were newly diagnosed with HCV infection during the index period. The age-standardized rate of newly-diagnosed HCV declined from over 50/100,000 (2003) to 15/100,000 (2012). This rate was highest in males from the FSU, particularly for birth cohorts in 1950-70. The study results suggest that the reported incidence of HCV infection in Israel is declining, while prevalence is particularly high among FSU immigrants and genotype 1 is predominant. As the HCV treatment landscape evolves, these estimates can inform future studies and health technology assessments. J. Med. Virol. 88:1044-1050, 2016. © 2015 Wiley Periodicals, Inc.
PMID: 26538137 [PubMed - in process]
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Role of Side Effects, Physician Involvement, and Patient Perception in Non-Adherence with Oral Bisphosphonates.

Goldshtein I, Rouach V, Shamir-Stein N, Yu J, Chodick G
Adv Ther
ABSTRACT
Related Articles
Role of Side Effects, Physician Involvement, and Patient Perception in Non-Adherence with Oral Bisphosphonates.
Adv Ther. 2016 Aug;33(8):1374-84
Authors: Goldshtein I, Rouach V, Shamir-Stein N, Yu J, Chodick G
Abstract
INTRODUCTION: The benefits of osteoporosis therapy are compromised by low adherence, thus requiring a better understanding of its barriers and unmet needs. The objective of this study was to assess reasons for non-adherence with oral bisphosphonates among osteoporotic women.
METHODS: A cross-sectional patient survey of women who initiated therapy with risedronate or alendronate between the years 2010 and 2012 were non-adherent [Medication Possession Ratio (MPR) <70%] or switched therapy within the first year. Survey participants were identified using Maccabi Health Services computerized database. Patients who gave informed consent completed a 20-min telephonic survey, assessing reasons for discontinuation or switching, including physician involvement, side effects, administration regimen, perceptions of bone health, and medications' efficacy.
RESULTS: The study population included 493 females (mean age = 66 ± 7) of whom 40% discontinued all anti-osteoporotic therapy (mean MPR = 19%), 9% remained on initial therapy (mean MPR = 47%), and 51% switched therapy (mean MPR = 62%). Family history, fracture history, socioeconomic status, and index drug class and frequency were similar in all groups. The most common reasons for switching or discontinuation of the first-line therapy were gastrointestinal side effects, such as heartburn, acid reflux or other (40.0%), and physician recommendation (26.7%). The major reasons for complete discontinuation of therapy were side effects (26.9%) and physician recommendation (20.0%). Perceived low importance was more commonly mentioned than high cost of medication (14% vs. 3%).
CONCLUSION: Our findings highlight the importance of low tolerability to non-adherence with osteoporosis therapy and underlines poor patients' awareness and sub-optimal physicians' involvement in conveying the importance of this therapy.
FUNDING: Merck & Co Inc.
PMID: 27329383 [PubMed - in process]
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Varda Shalev; +16 new citations

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16 new pubmed citations were retrieved for your search.
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Varda Shalev
These pubmed results were generated on 2017/07/04PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books.
Citations may include links to full-text content from PubMed Central and publisher web sites.
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Epidemiology of Amyotrophic Lateral Sclerosis: A Population-Based Study in Israel.

Weil C, Zach N, Rishoni S, Shalev V, Chodick G
Neuroepidemiology
ABSTRACT
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Epidemiology of Amyotrophic Lateral Sclerosis: A Population-Based Study in Israel.
Neuroepidemiology. 2016;47(2):76-81
Authors: Weil C, Zach N, Rishoni S, Shalev V, Chodick G
Abstract
BACKGROUND: Globally, the annual incidence and prevalence of amyotrophic lateral sclerosis (ALS) are estimated at 1.9 and 4.5 per 100,000 population, respectively. This study is aimed at describing the epidemiology of ALS in Israel in a real-world setting.
METHODS: A retrospective study was performed using the databases of Maccabi Healthcare Services (MHS), a 2-million-member health maintenance organization in Israel. The study included all MHS adults diagnosed with ALS between 1997 and 2013. In 2013, characteristics of ALS patients were compared to those of age-sex-matched patients without ALS. Survival after ALS diagnosis was assessed until death and until tracheostomy or death (follow-up through 2014).
RESULTS: In 2013 (n = 158), the prevalence of ALS was 8.1 per 100,000 population in MHS. In 1997-2013, a total of 375 ALS patients were diagnosed, corresponding to an average annual incidence of 1.8 per 100,000 population in MHS. The median survival from diagnosis to death was 3.5 years (95% CI 2.9-4.1), with approximately 28% surviving at least 10 years. Median tracheostomy-free survival was 2.5 years (95% CI 2.1-2.9).
CONCLUSIONS: Results suggest that there is a relatively high prevalence of ALS in Israel. Further research is needed to investigate factors that may contribute to the survival of patients with ALS in Israel.
PMID: 27617889 [PubMed - in process]
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Urinary albumin excretion with sitagliptin compared to sulfonylurea as add on to metformin in type 2 diabetes patients with albuminuria: A real-world evidence study.

Goldshtein I, Karasik A, Melzer-Cohen C, Engel SS, Yu S, Sharon O, Brodovicz K, Gadir N, Katzeff HL, Radican L, Chodick G, Shalev V, Tunceli K
J Diabetes Complications
ABSTRACT
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Urinary albumin excretion with sitagliptin compared to sulfonylurea as add on to metformin in type 2 diabetes patients with albuminuria: A real-world evidence study.
J Diabetes Complications. 2016 Sep-Oct;30(7):1354-9
Authors: Goldshtein I, Karasik A, Melzer-Cohen C, Engel SS, Yu S, Sharon O, Brodovicz K, Gadir N, Katzeff HL, Radican L, Chodick G, Shalev V, Tunceli K
Abstract
AIM: To compare the change in urinary albumin to creatinine ratio (UACR) in type 2 diabetes (T2DM) patients with albuminuria who initiate sitagliptin to those who initiate a sulfonylurea (SU) as add-on to metformin monotherapy.
METHOD: A cohort of T2DM patients with albuminuria (UACR >30mg/g) who initiated sitagliptin or SU as add-on dual therapy to metformin between 2008 and 2014 was extracted from the computerized medical records of a large managed care organization in Israel. Patients with albuminuria and UACR measurements available at treatment initiation and 120-365days afterwards were included. Propensity scores were calculated based on 17 factors, including demography, comorbidities, baseline levels of HbA1c, UACR, BMI, eGFR, and ACE/ARB use, and patients were matched in a 1:1 ratio. Changes in UACR were compared between the matched pairs using generalized estimating equations.
RESULTS: A total of 282 eligible pairs (sitagliptin:SU) were identified. During a mean follow-up of 9months, median UACR changes were -35% (IQR=-73% to 5%) and -31% (IQR=-72% to 21%) in the sitagliptin and SU groups, respectively. Mean absolute HbA1c reductions among sitagliptin and SU groups were 0.9% and 1.0%, respectively. The magnitude of UACR reduction generally increased with greater magnitude of HbA1c reduction in both treatment groups. However, after controlling for HbA1c reduction and the interaction between HbA1c reduction and UACR reduction, sitagliptin users demonstrated a trend toward an increased likelihood of UACR reduction compared to SU users (odds ratio=1.20; 95% confidence interval: 0.99-1.47, P=0.063).
CONCLUSION: Our results suggest that both sitagliptin and SU reduce albuminuria as an add-on therapy to metformin, but that sitagliptin may provide greater reductions in albuminuria independent of glycemic control when compared to SU. Larger population studies are required to further explore this.
PMID: 27320183 [PubMed - in process]
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Managing Osteoporosis: A Survey of Knowledge, Attitudes and Practices among Primary Care Physicians in Israel.

Fogelman Y, Goldshtein I, Segal E, Ish-Shalom S
PLoS One
ABSTRACT
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Managing Osteoporosis: A Survey of Knowledge, Attitudes and Practices among Primary Care Physicians in Israel.
PLoS One. 2016;11(8):e0160661
Authors: Fogelman Y, Goldshtein I, Segal E, Ish-Shalom S
Abstract
BACKGROUND: Osteoporosis is a systemic skeletal disorder characterized by impaired bone quality and microstructural deterioration leading to an increased propensity to fractures. This is a major health problem for older adults, which comprise an increasingly greater proportion of the general population. Due to a large number of patients and the insufficient availability of specialists in Israel and worldwide, osteoporosis is treated in large part by primary care physicians. We assessed the knowledge of primary care physicians on the diagnosis and treatment of osteoporosis.
METHODS: Physician's knowledge, sources of knowledge acquisition and self-evaluation of knowledge were assessed using a multiple choice questionnaire. Professional and demographic characteristics were assessed as well.
RESULTS: Of 490 physicians attending a conference, 363 filled the questionnaires (74% response rate). The physicians demonstrated better expertise in diagnosis than in medications (mechanism of action, side effects or contra-indications) but less than for other treatment related decisions. Overall, 50% demonstrated adequate knowledge of calcium and vitamin D supplementation, 51% were aware of the main therapeutic purpose of osteoporosis pharmacotherapy and 3% were aware that bisphosphonates should be avoided in patients with impaired renal function. Respondents stated frontal lectures at meetings as their main source of information on the subject.
CONCLUSION: The study indicates the need to intensify efforts to improve the knowledge of primary care physicians regarding osteoporosis, in general; and osteoporosis pharmacotherapy, in particular.
PMID: 27494284 [PubMed - in process]
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FRACTURE RISK ASSESSMENT WITH FRAX USING REAL-WORLD DATA: A POPULATION-BASED COHORT FROM ISRAEL.

Goldshtein I, Gerber Y, Ish-Shalom S, Leshno M
Am J Epidemiol
ABSTRACT
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FRACTURE RISK ASSESSMENT WITH FRAX USING REAL-WORLD DATA: A POPULATION-BASED COHORT FROM ISRAEL.
Am J Epidemiol. 2017 May 18;:
Authors: Goldshtein I, Gerber Y, Ish-Shalom S, Leshno M
Abstract
The predictive value of the WHO fracture risk assessment tool was evaluated using real-world community data. A population-based cohort of 141,320 women aged 50-90 years old (median age 58, inter quartile range (IQR): 54-67) at the year 2004 was extracted from the central database of a large Israeli healthcare services provider and insurer. Retrospective FRAX scores were calculated using computerized health records and compared to actual incident major osteoporotic fractures (MOF) during the following 10 years. A total of 6.9% and 2.2% MOF and hip fractures were expected vs. 13.5% and 2.9% observed. The area under receiver-operating characteristic curve (AUC) of FRAX without bone mineral density (BMD) was 0.65 (95% CI: 0.65, 0.66) for MOF and 0.82 (95% CI: 0.81, 0.82) for hip fracture. A total of 16,578 subjects had BMD data at index, and their risk estimates based solely on BMD exhibited lower predictive performance for MOF (AUC = 0.62 vs. 0.65, P value = 0.003) as well as hip fractures (AUC = 0.78 vs. 0.84, P value < 0.001) as compared with FRAX. FRAX using electronic health records provided reasonable discrimination despite some underestimation of the absolute risk of non-hip fractures. Integration with routine clinical systems could increase implementation in daily practice and improve risk detection, especially for patients without BMD.
PMID: 28520844 [PubMed - as supplied by publisher]
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Adherence With Bisphosphonates and Long-Term Risk of Hip Fractures: A Nested Case-Control Study Using Real-World Data.

Shalev V, Sharman Moser S, Goldshtein I, Yu J, Weil C, Ish-Shalom S, Rouach V, Chodick G
Ann Pharmacother
ABSTRACT
Related Articles
Adherence With Bisphosphonates and Long-Term Risk of Hip Fractures: A Nested Case-Control Study Using Real-World Data.
Ann Pharmacother. 2017 May 01;:1060028017710482
Authors: Shalev V, Sharman Moser S, Goldshtein I, Yu J, Weil C, Ish-Shalom S, Rouach V, Chodick G
Abstract
BACKGROUND: Hip fracture is a major complication of osteoporosis. Bisphosphonate medication is the mainstay of treatment for osteoporosis. However, concerns have been raised regarding the effectiveness of bisphosphonates in reducing hip fracture risk after long-term use, particularly among patients with suboptimal adherence.
OBJECTIVE: To examine the association between adherence with bisphosphonate therapy and long-term risk of hip fracture.
METHODS: Included in the present nested case-control study were osteoporotic women (n = 14 357) who initiated bisphosphonate therapy in 2000-2010 and were retrospectively followed for incident hip fracture through November 2014. Within this cohort, each case of primary hip fractures was individually matched to 3 controls without a primary hip fracture. Proportion of follow-up days covered (PDC) with bisphosphonates was calculated from bisphosphonate purchases. Adherence was categorized into the following groups: purchase of 1 or 2 months' supply (reference group), at least 3 months' supply to PDC ≤20%, PDC >20% to ≤80%, PDC >80% to ≤100%.
RESULTS: Included in the analysis were 426 case-control groups with a mean age (SD) of 73.7 years (7.9). Compared with the reference group, PDC of 80% to 100% with bisphosphonates was associated with a significant reduction in hip fracture risk for patients with 8 to 15 years of follow-up (OR = 0.39; 95% CI = 0.18-0.87). Among patients with a follow-up of up to 3 years, OR was 0.58 (95% CI = 0.31-1.06).
CONCLUSIONS: Adherence with bisphosphonates among osteoporotic patients is associated with lower risk of hip fracture, with no indication of diminished effectiveness with long-term use.
PMID: 28535690 [PubMed - as supplied by publisher]
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Differences in short and long-term survival between males and females with new-onset heart failure: A retrospective cohort study.

Chodick G, Weitzman D, Blaustein RO, Shalev V, Bash LD
Eur J Intern Med
ABSTRACT
Related Articles
Differences in short and long-term survival between males and females with new-onset heart failure: A retrospective cohort study.
Eur J Intern Med. 2017 Jun;41:e21-e23
Authors: Chodick G, Weitzman D, Blaustein RO, Shalev V, Bash LD
PMID: 28336125 [PubMed - in process]
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Comprehensive healthcare resource use among newly diagnosed congestive heart failure.

Bash LD, Weitzman D, Blaustein RO, Sharon O, Shalev V, Chodick G
Isr J Health Policy Res
ABSTRACT
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Comprehensive healthcare resource use among newly diagnosed congestive heart failure.
Isr J Health Policy Res. 2017;6:26
Authors: Bash LD, Weitzman D, Blaustein RO, Sharon O, Shalev V, Chodick G
Abstract
BACKGROUND: Congestive heart failure (CHF) is among the most common causes of hospital admissions and readmissions in the Western world. However, the burden of ambulatory care has not been as well investigated. The objective of this study was to assess the relative burden and direct medical costs of CHF including inpatient and outpatient care.
METHODS: We used longitudinal clinical data from a two-million member health organization in Israel (Maccabi Healthcare Services) to identify adults with newly diagnosed CHF between January 2006 and December 2012, either in the in- or outpatient setting. Adults without CHF were age- and sex-matched to CHF patients and healthcare utilization and all modes of healthcare costs were compared among them, excluding those in their last year of life.
RESULTS: The burden posed by 6592 CHF patients was significantly (p < 0.001) larger than that of 32,960 matched controls. CHF patients had significantly higher rates of baseline comorbidity and healthcare utilization compared to non-CHF controls. This was evident in all categories of healthcare services and expenses, including in- and outpatient visits, laboratory expenses, medication costs, among younger and older, men and women. Among those who incurred any healthcare costs, younger (45-64y) and older (65 + y) subjects with CHF were observed to have about 3.25 (95% CI: 2.96-3.56) and 2.08 (95% CI: 1.99-2.17) times the healthcare costs, respectively, compared to subjects without CHF after adjusting for patient characteristics.
CONCLUSION: CHF is associated with an overall two- to three-fold higher cost of healthcare services depending on patient age, accounting for over half of all healthcare costs incurred by elderly CHF patients, and more than two-thirds of all costs among younger CHF patients. Observations of the large burden posed on one of the youngest societies in the developed world are profound, implicative of great opportunities to control the costs of CHF. Further research to understand how resource use impacts health outcomes and quality of care is warranted.
PMID: 28593038 [PubMed - in process]
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Gabriel Chodick; +28 new citations

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28 new pubmed citations were retrieved for your search.
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Gabriel Chodick
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Epidemiological analyses

Back-to-School Upper Respiratory Infection in Preschool and Primary School-Age Children in Israel.

Perry Markovich M, Glatman-Freedman A, Bromberg M, Augarten A, Sefty H, Kaufman Z, Sherbany H, Regev L, Chodick G, Mendelson E, Shohat T, Mandelboim M, Israel Pediatric Upper Respiratory Infection Network (IPURIN)
Pediatric Infectious Disease Journal 2015;34:476–481
ABSTRACT
Background: Increased upper respiratory infection (URI) among children at the beginning of school year is well known to parents and pediatricians. However, this phenomenon is not well documented or characterized.
Methods: Computerized datasets from a large health maintenance organization in Israel were used to calculate the weekly rates of URI among children 3–14 years old for the years 2007–2012. In addition, nasopharyngeal swabs were collected in 2010–2012 from children with URI symptoms and controls during school opening time. Swabs were tested by real-time polymerase chain reaction for the presence of respiratory viruses.
Results: Time-series analysis demonstrated a peak of URI in September each year. The peaks reached their height 2 weeks after school opening and returned to baseline within 4–7 weeks. The main 3 viruses detected both in URI patients and in healthy controls during the first weeks of school opening were rhinovirus, adenovirus and enterovirus. The detection rate of any respiratory virus, and of rhinovirus in particular, was significantly higher among cases than among controls (54% vs. 16%, P < 0.001 for any virus, and 35% vs. 6.0%, P < 0.01 for rhinovirus). When adjusting for age and sex cases had 5.8 times more viral detection when compared with controls. Upper respiratory symptoms were significantly more prevalent among the virus-positive cases when compared with negative ones.
Conclusions: Back-to-school illness consisting of URI has a distinct epidemiological pattern demonstrating a rapid rise peaking within 2 weeks of school opening and is associated predominantly with rhinovirus.
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Decline in estimated glomerular filtration rate and subsequent risk of end-stage renal disease and mortality.

Coresh J, Turin TC, Matsushita K, Sang Y, Ballew SH, Appel LJ, Arima H, Chadban SJ, Cirillo M, Djurdjev O, Green JA, Heine GH, Inker LA, Irie F, Ishani A, Ix JH, Kovesdy CP, Marks A, Ohkubo T, Shalev V, Shankar A, Wen CP, de Jong PE, Iseki K, Stengel B, Gansevoort RT, Levey AS, CKD Prognosis Consortium
JAMA In Press
ABSTRACT
Related Articles
Decline in estimated glomerular filtration rate and subsequent risk of end-stage renal disease and mortality.
JAMA. 2014 Jun 25;311(24):2518-31
Authors: Coresh J, Turin TC, Matsushita K, Sang Y, Ballew SH, Appel LJ, Arima H, Chadban SJ, Cirillo M, Djurdjev O, Green JA, Heine GH, Inker LA, Irie F, Ishani A, Ix JH, Kovesdy CP, Marks A, Ohkubo T, Shalev V, Shankar A, Wen CP, de Jong PE, Iseki K, Stengel B, Gansevoort RT, Levey AS, CKD Prognosis Consortium
Abstract
IMPORTANCE: The established chronic kidney disease (CKD) progression end point of end-stage renal disease (ESRD) or a doubling of serum creatinine concentration (corresponding to a change in estimated glomerular filtration rate [GFR] of −57% or greater) is a late event.
OBJECTIVE: To characterize the association of decline in estimated GFR with subsequent progression to ESRD with implications for using lesser declines in estimated GFR as potential alternative end points for CKD progression. Because most people with CKD die before reaching ESRD, mortality risk also was investigated.
DATA SOURCES AND STUDY SELECTION: Individual meta-analysis of 1.7 million participants with 12,344 ESRD events and 223,944 deaths from 35 cohorts in the CKD Prognosis Consortium with a repeated measure of serum creatinine concentration over 1 to 3 years and outcome data.
DATA EXTRACTION AND SYNTHESIS: Transfer of individual participant data or standardized analysis of outputs for random-effects meta-analysis conducted between July 2012 and September 2013, with baseline estimated GFR values collected from 1975 through 2012.
MAIN OUTCOMES AND MEASURES: End-stage renal disease (initiation of dialysis or transplantation) or all-cause mortality risk related to percentage change in estimated GFR over 2 years, adjusted for potential confounders and first estimated GFR.
RESULTS: The adjusted hazard ratios (HRs) of ESRD and mortality were higher with larger estimated GFR decline. Among participants with baseline estimated GFR of less than 60 mL/min/1.73 m2, the adjusted HRs for ESRD were 32.1 (95% CI, 22.3-46.3) for changes of −57% in estimated GFR and 5.4 (95% CI, 4.5-6.4) for changes of −30%. However, changes of −30% or greater (6.9% [95% CI, 6.4%-7.4%] of the entire consortium) were more common than changes of −57% (0.79% [95% CI, 0.52%-1.06%]). This association was strong and consistent across the length of the baseline period (1 to 3 years), baseline estimated GFR, age, diabetes status, or albuminuria. Average adjusted 10-year risk of ESRD (in patients with a baseline estimated GFR of 35 mL/min/1.73 m2) was 99% (95% CI, 95%-100%) for estimated GFR change of −57%, was 83% (95% CI, 71%-93%) for estimated GFR change of −40%, and was 64% (95% CI, 52%-77%) for estimated GFR change of −30% vs 18% (95% CI, 15%-22%) for estimated GFR change of 0%. Corresponding mortality risks were 77% (95% CI, 71%-82%), 60% (95% CI, 56%-63%), and 50% (95% CI, 47%-52%) vs 32% (95% CI, 31%-33%), showing a similar but weaker pattern.
CONCLUSIONS AND RELEVANCE: Declines in estimated GFR smaller than a doubling of serum creatinine concentration occurred more commonly and were strongly and consistently associated with the risk of ESRD and mortality, supporting consideration of lesser declines in estimated GFR (such as a 30% reduction over 2 years) as an alternative end point for CKD progression.
PMID: 24892770 [PubMed - indexed for MEDLINE]
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Factors Associated With Time to Diagnosis in Fibromyalgia

Chodick G, Weitzman D, Bar-On Y, Shalev V, Amital H.
Journal of Patient-Centered Research and Reviews. 2015; 2(2).
ABSTRACT
Background/Aims: The diagnosis of fibromyalgia, a chronic debilitating disorder, is complicated and affected by various factors of the patient and the caregiver. The objectives of this study were to investigate the time passing from initial complaints to diagnosis and to delineate the patient and physician characteristics affecting that time.

Methods: For this retrospective cohort study we used the datasets of Maccabi Health Services (MHS), the second largest health maintenance organization in Israel. We identified all confirmed cases of fibromyalgia that were diagnosed by specialists in the community or hospital during 1/2008–12/2011. These patients were compared to sex- and-age-matched fibromyalgia-free members. Different complaint patterns were examined to ascertain time of initial complaints. The pattern with the best validity was applied on nonvalidated cases that were diagnosed with fibromyalgia by primary physician, rheumatologist or at release from hospitalization during the same period. Patient and primary physician factors associated with time between initial complaints and fibromyalgia diagnosis were assessed. A multilevel generalized mixed linear model with a log-linked gamma distribution was used to account for clustering of patients associated with the same primary physician.

Results: Our study included 2,656 confirmed cases of fibromyalgia (91% women, mean age: 51.1 years, standard deviation [SD]: 11.3 years). The most valid initial complaints pattern included 4 or more complaints within 6 months, found in 73% of the cases. These results indicated that the mean duration between initial fibromyalgia-related complaints to final diagnosis was 4.7 years with SD of 3.6 years. In a multivariable model, shorter time to diagnosis was associated with patients of young age, male gender and higher socio-economic status, and with primary physicians of young age, family/pediatric/internal specialty versus general, and medical studies in Eastern or Western Europe versus other continents.

Discussion: The mean time to diagnosis of fibromyalgia is very long and is significantly influenced by patient and physician characteristics. Better patient and physician education, and increased awareness to the disease and its early complaints, can be a key for improving the diagnosis of fibromyalgia.

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Osteoporosis in the community: Findings from a novel computerized registry in a large health organization in Israel

Goldshtein I, Chandler J, Shalev V, Ish –Shalom S, Nguyen A.M, Rouach V, Chodick G.
Journal of Aging Research & Clinical Practice. 2015;in press
ABSTRACT
Background: Osteoporosis is a growing public health concern due to its rising prevalence and excess morbidity and mortality. Automated patient registries have gained great importance in health and disease management of major chronic diseases, but are rarely used in osteoporosis.

Objectives: To construct an automated, population-based registry of osteoporosis. Setting: The electronic medical records and pharmacy databases of a 2 million member health organization in Israel (Maccabi Healthcare Services).

Methods: Included in the registry were adults who were diagnosed with osteoporosis diagnosis, had major osteoporotic fractures, or purchased relevant medications, between 2000 and 2013. In addition, we included patients with low bone density as extracted from over 140,000 measurements reports, using an automated optical character recognition (OCR) system. Two-thirds of the cases were validated by more than one inclusion criterion.

Results: A total of 118,141 osteoporosis patients were identified. The point prevalence of osteoporosis among members aged 50 or above in 2013 was 19%. The mean age at registry entry was 62 (SD=12) and 66 (SD=14) years for females and males, respectively. The highest annual risk of developing osteoporosis (27 per 1000) was recorded among females aged 65-75. In 28% of the patients, there was no indication of treatment with osteoporosis therapy.

Conclusions: To the best of our knowledge, this is one of the first real-world automated registries of osteoporosis. Similar registries may provide valuable data for real-time monitoring of trends, quality of care, and outcome research in osteoporosis and its complications.
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0276 The role of various predictors of seizure recurrence in assignment of young men to professions with associated exposure to (seizure) risk factors.

Tavor M, Neufeld MY, Chodick G, Zack O, Moshe S.
Occupational and Environmental Medicine. 2014;71 Suppl 1:A99.
ABSTRACT
Objectives: To study the risk of epileptic seizures as a function of disease severity and occupational stress (physical and mental) in new military recruits in the Israel Defense Forces (IDF).

Method: The medical records of over 145 000 18-year old men, recruited to the IDF between the late-nineties and early two-thousands, were used to assemble a cohort, which was followed for a period of 36 months. The severity of the disease was determined according to 5 categories. Recruits were subdivided according to the following occupational categories: Combat Units (CU), Maintenance Units (MU) and Administrative Units (AU).
Results The annual incidence rate for a first seizure was 26/100 000. The rates in CU and MU were lower than AU (0.41 and 0.81 vs. 1 respectively, p < 0.01). Similar findings were found in other disease categories.

Conclusions: The low rate for a first seizure and the lower overall seizure rate in CU compared to MU and AU may be explained by the recruiting of a healthy population, higher motivation than before, and meticulous adherence to diagnostic criteria. The higher recurrence rate in our research as compared to the previous follow up, may be attributable to the modification of disease categories. Our findings suggest moderating occupational restrictions for epilepsy patients and using EEG and relapse-free periods of 2–6 years as fitness for work criteria. We propose the reassessment of severity criteria currently used by the IDF.
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0372 Patients' views and expectations on social work services in the occupational medicine clinic in the Maccabi Health service organisation.

Moshe S, Tzinamon T, Chodick G, Zack O, Tal M.
Occupational and Environmental Medicine. 2014;71 Suppl 1:A111-2.
ABSTRACT
OBJECTIVES: To explore patients' expectations regarding the social work service and to deterrmine their satisfaction level with the care provided to them so far by the social worker in the framework of the occupational clinic.

METHOD: This is a cross-sectional study which consists of Maccabi members of working age that visited occupational nedicine departments between September 2011 and July 2012 for the purpose of fitness-for-work evaluation who were referred to and met with a social worker. These members filled out an expectation and satisfaction questionnaire after meeting with the social worker.

RESULTS: A total of 203 questionnaire were filled out. Most of the patients were interested in receiving information about their benefits (85%). A smaller number of patients (39.2%) were interested in receiving help dealing with a family members' distress due to the loss of work ability of the patient. A very high percentage of the patients (97%) were satisfied with the social worker session. A correlation was found between the patients' expectations and their satisfaction with the amount of information they received (p > 0.01).

CONCLUSIONS: This is a first study of this kind addressing social work services in a public occupational medicine services. The study shows the positive advantage of this service and a high patient satisfaction level with the social work service. The satisfaction level was high even though the patients' health status was relatively low. We recommend expanding the service beyond Maccabi onto other health service organisations.
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Childhood overweight or obesity increases the risk of IIH recurrence fivefold

Stiebel-Kalish H, Serov I, Sella R, Chodick G, Snir M.
International Journal of Obesity. 2014;38(11):1475-7.
ABSTRACT
Overweight and obesity are less closely associated with idiopathic intracranial hypertension (IIH) in young children than in post-pubescent children and adults. We examined the hypothesis that being overweight or obese (body mass index (BMI) greater than or equal to85th percentile) in children is a risk factor for IIH recurrence. A total of 43 children with IIH who were followed up for an average of 9±3.4 years were evaluated in a retrospective case–control series. The rate of IIH recurrence was compared between children of healthy weight and children presenting with overweight or obesity, using survival curve analysis. The overall risk for long-term IIH recurrence in children is ~20%. Following weight stratification, the risk for IIH recurrence in our cohort was fivefold higher in children with a BMI greater than or equal to85th percentile (57%) than in healthy weight children (11%; log-rank test P=0.04). Pediatricians may consider counseling families that weight control may be a means of decreasing the risk of IIH recurrence.
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Red blood cell distribution width and the risk of cardiovascular morbidity and all-cause mortality. A population-based study.

Arbel Y, Weitzman D, Raz R , Steinvil A, Zeltser D, Berliner B, Chodick G, Shalev V.
Thrombosis and Haemostasis 2014;111:300-7
ABSTRACT
Introduction: 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.

Methods: We utilized the computerized database of a large community based healthcare maintenance organization (HMO)in Israel to identify a cohort of 254,473 eligible patients aged 40 or above that performed a blood count during 2006. We evaluated the relationship of RDW values for major adverse cardiac events (MACE) and all-cause mortality over a period of 5 years.

Results: During a total of 1.4 million person-years, a total of 23,949 incident cases of MACE and 5236 deaths were documented In a multivariable model, a positive dose response relationship between RDW level and all caused mortality or MACE was found. Compared to patients with a RDW of 12% or lower, patients with RDW>17% had a hazard ratio of 8.2 (95% CI: 4.4-15.2, P<0.001) for all-cause mortality and 1.32 (95% CI: 1.09-1.64, p<0.001) for MACE.

Conclusion: RDW level of 12% and above is significantly associated with an increased risk of cardiovascular morbidity and all-cause mortality
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Incidence Trends of Keratinocytic Skin Cancers and Melanoma in Israel 2006-2011

Sella T, Goren1, Shalev V, Shapira H, Zandbank J, Rosenblum J, Kimlin MG, Chodick G.
British Journal of Dermatology In Press
ABSTRACT
BACKGROUND:
The incidence of melanoma and keratinocyte cancers (KCs) is rising worldwide. Squamous cell carcinomas (SCCs) and basal cell carcinoma (BCCs) are the most common of all cancers.

OBJECTIVES:
To determine trends in the incidence of melanoma, BCC and SCC among 1·7 million members of Maccabi Healthcare Services (MHS) from 2006 to 2011.

METHODS:
Data on patients newly diagnosed with melanoma, SCC and BCC were collected from the MHS Cancer Registry and based on histology reports from the centralized pathology laboratory. Age-specific and overall age-adjusted European standardized rates were computed. Trends were estimated by calculating average annual percentage change (AAPC).

RESULTS:
During the 6-year study period, 16 079 patients were diagnosed with at least one BCC, 4767 with SCC and 1264 with invasive melanoma. Age-standardized incidence rates were 188, 58 and 17 per 100 000 person years for BCC, SCC and melanoma, respectively. All lesions were more common among men and primarily affected the elderly. BCC rates were stable throughout the study period [AAPC -0·7%, 95% confidence interval (CI) -4·5 to 3·2], while the incidence of SCC increased significantly (AAPC 15·5%, 95% CI 2·6-30·0). In contrast, melanoma rates continuously decreased (AAPC -3·0%, 95%CI -4·5 to -0·1).

CONCLUSIONS:
The incidence of KC in Israel is high. The disparities in incidence trends between SCC, BCC and melanoma allude to their different aetiologies. These findings underscore the importance of continuous monitoring, education and prevention programmes in a growing high-risk population.
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Gestational diabetes and the risk of cryptorchidism and hypospadias.

Trabert B, Chodick G, Shalev V, Sella T, Longnecker MP, McGlynn KA.
Epidemiology. 2014;25:152-3
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Third-generation ELISA Thyrotropin-Receptor Antibody Levels as an Adjuvant Tool to Guide Management of Patients with Graves' Orbitopathy

Tvito-Green R, Reich E, Robenshtok E, Chodick G, Ron-Kella Y, Stiebel-Kalish H.
Endocrine Practice. 2014;20:145-9.
ABSTRACT
Objective: When assessing patients with Graves orbitopathy (GO) in an endocrinology outpatient setting, it is desirable to have a diagnostic laboratory tool to complement the clinical activity score (CAS) in distinguishing patients with moderate-severe active GO requiring high-priority ophthalmological care from those with mild or inactive GO who can be electively scheduled and to asses response to treatment.

Methods: A retrospective study was conducted to evaluate the correlation between thyrotropin-receptor antibody (TRAb)-Fast-enzyme-linked immunosorbent assay (ELISA) results and CAS in patients with GO seen at a tertiary referral center between 2000 and 2009. TRAb levels were quantified using a commercial third-generation TRAb-specific ELISA. Other variables analyzed included smoking status, gender, age, and thyroid-stimulating hormone level.

Results: Fifty-five patients with GO had a documented CAS within a mean of 22 days from the recorded TRAb level determined by TRAb-Fast-ELISA. An increase in TRAb-Fast-ELISA of 1 unit was associated with a 15% (95% confidence interval, 7-24%) increase in the odds ratio of elevated CAS. A TRAb-Fast-ELISA result ≥10 as a diagnostic tool to predict a CAS ≥3 was assessed and was found to have a specificity of 86.7% and a sensitivity of 87.2% for moderately severe GO.

Conclusion: Our results demonstrate the ability to predict a patient's GO activity level by antibody titer. A TRAb-Fast-ELISA result ≥10 can be used as a complementary diagnostic tool to predict a CAS ≥3.
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Prevalence and factors associated with resistant hypertension in a large health maintenance organization in Israel.

Weitzman D, Chodick G, Shalev V, Grossman C, Grossman E.
Hypertension. In Press
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The Maccabi Glaucoma Study: prevalence and incidence of glaucoma in a large israeli health maintenance organization.

Levkovitch-Verbin H, Goldshtein I, Chodick G, Zigman N, Shalev V.
American Journal of Ophthalmology. In Press
ABSTRACT
PURPOSE:
To investigate the prevalence and incidence of glaucoma in a large health maintenance organization (HMO) in Israel.

DESIGN:
A population-based retrospective cohort study, conducted using electronic medical database.

METHODS:
Collected data included personal and medical characteristics.

SETTING:
Maccabi Healthcare Services, the second-largest HMO in Israel, insuring 2 million members and serving 25% of the population with a nationwide distribution.

STUDY POPULATION:
Maccabi members from January 2003 to December 2010.

MAIN OUTCOME MEASURES:
Prevalence and incidence of glaucoma according to the International Classification of Diseases, 9th revision, Clinical Modification diagnostic codes.

RESULTS:
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 6674 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<.01) higher in men in older ages.

CONCLUSIONS:
Glaucoma affects nearly 10% of the elderly population in Maccabi, with the highest risk of diagnosis at age 70-74. Since glaucoma leads to irreversible vision loss, the present estimates of morbidity should be of significant concern.
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In Vitro Fertilization and Risk of Breast and Gynecologic Cancers: A Retrospective Cohort Study within the Maccabi Healthcare Services

Brinton L, Trabert B, Lunnenfeld E, Sella T, Shalev V, Chodick G.
Fertility and Sterility 2013;99:1189-96.
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.
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The Invisible Patient: Characteristics of Elderly People who do not visit Primary Care Physicians

Eshel N, Raz R, Chodick G, Guindy M.
The Israel Journal of Health Policy Research 2013;2:7
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A prospective study of the patterns and dynamics of colonization with Candida spp. in very low-birth weight neonates

Leibovitz E,.Lifshitz-Riven I, Borer A, Taraboulos-Klein T, Zamir O, Shani E, Melamed R, Flidel Rimon O, Bradenstein R, Chodick G, Golan A.
Scandinavian Journal of Infectious Diseases 2013;45:842-8
ABSTRACT
Background: Knowledge of fungal colonization patterns in very low birth weight infants (VLBWI) admitted to the neonatal intensive care unit (NICU) is essential in understanding the process of fungal infections in neonates. We analyzed prospectively, during 2009–2010, the patterns and dynamics of fungal colonization in VLBWI, including timing, colonization sites, and species involved. Methods: Weekly skin, oropharynx, and rectum/stool surveillance fungal cultures were collected from admission until discharge in VLBWI in the NICU. None received antifungal prophylaxis. Results: Overall, 118 VLBWI provided 1723 samples; 34 (29%) had 104 positive samples at least once during the first 10 hospitalization weeks. Thirty-nine (33%) weighed < 1000 g; 68 were delivered by cesarean section. Candida albicans (57/104, 55%) and Candida parapsilosis (26/104, 25%) were the main fungi isolated. Eight (24%) VLBWI were colonized during the first week and 23 (68%) during the second week. No differences in colonization were recorded between cesarean section and vaginally delivered VLBWI. The colonization risk at least once during the first 10 weeks was 23% for skin, 14% for oropharynx, 27% for rectum/stool, and 38% for any anatomic site sampled. Persistent colonization was recorded in 5/34 (15%), while transient colonization was found in 14/34 (41%) VLBWI; 16/34 (47%) were discharged or died colonized with Candida spp. Candidemia was diagnosed in 4 (3%) VLBWI and previous/simultaneous colonization was found in 3/4. Conclusions: The cumulative risk of colonization, at any sampled site and at least once during follow-up, was high. Initial colonization occurred most often during the first 2 weeks of life. Colonization dynamics were characterized by various persistence, disappearance, and recolonization patterns. Candidemia was rare.

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Continuation of statin therapy and primary prevention of nonfatal cardiovascular events.

Shalev V, Goldstein I, Porath A, Weitzman D, Shemer J, Chodick G.
American Journal of Cardiology 2012;110:1779-86.
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Prevalence of Epilepsy and Attention Deficit/Hyperactivity Disorder: A population-based study.

Cohen R, Senecky Y, Inbar D, Chodick G, Shalev V, Shuper A, Raz R.
Journal of Child Neurology 2012 in press
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Evaluating the epidemiology and morbidity burden associated with human papillomavirus in Israel: accounting for CIN1 and genital warts in addition to CIN2/3 and cervical cancer.

Shavit O, Raz R, Stein M, Chodick G, Schejter E, Ben-David Y, Cohen R, Arbel D, Shalev V
Appl Health Econ Health Policy. 2012 Mar 1;10(2):87-97
ABSTRACT
BACKGROUND: Human papillomavirus (HPV) infection is mostly associated with cervical cancer (CC). However, it can cause other illnesses as well, all of which impact on people's wellbeing and consume healthcare resources. Measures for prevention or early detection of these conditions differ in their effectiveness and cost. An informative evaluation of the projected benefit of these measures depends on understanding the current unmet need, not only limited to CC.

OBJECTIVE: To evaluate the burden of HPV-related conditions in Israel, including CC, cervical precancerous lesions and genital warts.

METHODS: A retrospective database analysis was conducted for the second largest health management organization (HMO) in Israel, covering approximately 1.8 million people. Records were drawn following a search for key words indicative of related diagnoses, lab results, medications, or procedures for the time period of 2006-2008. Prevalence, incidence and resource utilization were analysed. Findings were extrapolated to the whole Israeli population using age and gender incidence rates.

RESULTS: Incidence of CC was found to be 5 per 100,000 females. Incidences of cervical intraepithelial neoplasia (CIN) grades 1, 2 and 3 were 74, 27 and 36 per 100,000 females, respectively. Incidence of genital warts was 239 and 185 per 100,000 for men and women, respectively. The overall annual economic burden was calculated to be $US48,838,058 (year 2010 values).

CONCLUSIONS: HPV poses a significant burden in terms of health (clinical and quality of life) and in monetary terms, even for conditions that are sometimes regarded as benign, such as CIN1 or genital warts. Current findings should be used for proper evaluation of measures to reduce HPV-related morbidity and mortality, such as regular screening and vaccination.

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Chronic urticaria and autoimmunity: Associations found in a large population study.

Confino-Cohen R, Chodick G, Shalev V, Leshno M, Kimhi O, Goldberg A
J Allergy Clin Immunol. 2012 Feb 13.
ABSTRACT
BACKGROUND: Chronic urticaria (CU) is a common disease in which most cases were considered to be idiopathic. Recent evidence indicates that at least a subset of cases of chronic idiopathic urticaria are autoimmune in origin.

OBJECTIVE: We aimed to characterize the association between CU, autoimmune diseases, and autoimmune/inflammatory serologic markers in a large unselected population.

METHODS: Data on 12,778 patients given a diagnosis of CU by either allergy or dermatology specialists during 17 years in a large health maintenance organization in Israel were collected. For each patient, we collected information on diagnosis of major, well-defined autoimmune diseases and autoimmunity- and inflammatory-related serologic markers. Similar data were collected for a control group comprised of 10,714 patients who visited dermatologists, family physicians, or allergy specialists and had no indication of CU.

RESULTS: Having CU was associated with an increased odds ratio for hypothyroidism, hyperthyroidism, and antithyroid antibodies. Female patients with CU had a significantly higher incidence of rheumatoid arthritis, Sjögren syndrome, celiac disease, type I diabetes mellitus, and systemic lupus erythematosus, mostly diagnosed during the 10 years after the diagnosis of CU. High mean platelet volume, positive rheumatoid factor, and antinuclear antibodies were all significantly more prevalent in patients with CU.

CONCLUSIONS: A strong association was found between CU and major autoimmune diseases. A common pathogenic mechanism is implied by the high prevalence of autoantibodies and the existence of a chronic inflammatory process expressed by the high mean platelet volume. These findings have implications for the diagnosis, management, and prognosis of patients with CU
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Osteocalcin is independently associated with body mass index in adolescent girls.

Dubnov-Raz G, Ish-Shalom S, Chodick G, Rozen GS, Giladi A, Constantini NW.
Pediatric Obesity 2012;7:313-318
ABSTRACT
Objective
Osteocalcin is a bone-related protein, recently found to correlate with body mass index (BMI), waist circumference, fat percentage and metabolic syndrome in adults. The aim of this study was to determine the relationship between osteocalcin and BMI in adolescence, a time of significant bone accrual, while considering possible confounders related to bone and body composition.

Methods
We analyzed data from 160 female adolescents (mean age 15.1 ± 0.7 years), which were divided into tertiles by osteocalcin levels. Across these three groups, we examined the differences in BMI with relation to age, total daily energy intake, calcium intake, physical activity (PA), total body bone mineral density, parathyroid hormone (PTH), 25(OH)-vitamin D, bone alkaline phosphatase and body fat percentage.

Results
Mean BMI values differed significantly between participants in the three osteocalcin tertiles, including after adjustment for age, PA, PTH, energy and calcium intakes. Post-hoc analysis revealed that girls in the highest osteocalcin tertile, had a significantly lower BMI than those in the two lower ones (19.3 ± 2.2 vs. 20.6 ± 3.0 and 20.7 ± 2.9 kg m−2, respectively, P = 0.018). There was no significant difference in energy and calcium intakes, bone mineral density, 25(OH)-vitamin D levels and PTH between study groups.

Conclusions
In female adolescents, BMI is inversely related to osteocalcin, even after consideration of several factors that may affect bone and fat mass. As bone mineral density, 25(OH)D and PTH did not differ between groups, it is possible that the relation between osteocalcin and BMI could be unrelated to bone tissue itself.
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Vitamin D deficiency prevalence and cardiovascular risk in Israel

Steinvil A, Leshem-Rubinow E, Berliner S, Justo D, Finn T, Ish-shalom M.
European Journal of Clinical Investigation. 2011;41:263-268
ABSTRACT
Background: Accumulated data in the past years suggest that vitamin D deficiency has an adverse effect on
cardiovascular (CVD) health and that its prevalence is significantly higher among patients with CVD risk factors,
contributing to the pathogenesis of CVD.
Materials and methods: This is a cross-sectional analysis of a relatively large database derived from a health
care maintenance organization. The population consisted of individuals 18 years and older who had undergone
blood tests for vitamin D levels for any reason during 2001–2008.
Results: The study population consisted of 34 874 individuals: 26 699 (76Æ6%) were women at a mean ± SD
age of 55 ± 15 and 8175 men (23Æ4%) aged 55 ± 17. The mean ± SD vitamin D level was 23Æ2 ± 10Æ1 and
22Æ7 ± 9Æ9 for men and women, respectively. The prevalence of vitamin D deficiency or insufficiency (vitamin D
levels < 30 ng mL)1) for the entire study population was surprisingly high for men and women (79Æ2% and
77Æ5%, respectively). This remained consistent with only little variation when stratified by age. The group with
vitamin D < 15 ng mL)1 vs. the group with vitamin D levels ‡ 30 ng mL)1 demonstrated a significant
(P < 0Æ031) age-adjusted odds ratios for the presence of hypertension, diabetes mellitus, dyslipidemia, obesity
and peripheral vascular disease for women (OR = 1Æ19; 1Æ65; 1Æ13; 2Æ28; 1Æ85, respectively), and the presence of all the above except hypertension in men (OR = 1Æ51; 1Æ28; 2Æ06; 1Æ73, respectively).
Conclusions: Vitamin D deficiency is associated with CVD and other risk factors in this Israeli study population.
The prevalence of the deficiency in Israel is similar to the prevalence found in less sunny regions.
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Comparing three basic models for seasonal influenza.

Edlund S, Kaufman J, Lessler J, Douglas J, Bromberg M, Kaufman Z, Bassal R, Chodick G, Marom R, Shalev V, Mesika Y, Ram R, Leventhal A.
Epidemics. 2011 Sep;3(3-4):135-42. doi: 10.1016/j.epidem.2011.04.002.
ABSTRACT
In this paper we report the use of the open source Spatiotemporal Epidemiological Modeler (STEM, www.eclipse.org/stem) to compare three basic models for seasonal influenza transmission. The models are designed to test for possible differences between the seasonal transmission of influenza A and B. Model 1 assumes that the seasonality and magnitude of transmission do not vary between influenza A and B. Model 2 assumes that the magnitude of seasonal forcing (i.e., the maximum transmissibility), but not the background transmission or flu season length, differs between influenza A and B. Model 3 assumes that the magnitude of seasonal forcing, the background transmission, and flu season length all differ between strains. The models are all optimized using 10 years of surveillance data from 49 of 50 administrative divisions in Israel. Using a cross-validation technique, we compare the relative accuracy of the models and discuss the potential for prediction. We find that accounting for variation in transmission amplitude increases the predictive ability compared to the base. However, little improvement is obtained by allowing for further variation in the shape of the seasonal forcing function.

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Gestational diabetes and risk of incident primary cancer: a large historical cohort study in Israel

Sella T, Chodick G, Barchana M, Heymann AD, Porath A, Kokia E, Shalev V.
Cancer Causes Control 2011 Nov;22(11):1513-20. Epub 2011 Aug 17
ABSTRACT
PURPOSE: Gestational diabetes mellitus (GDM), a state of glucose intolerance associated with pregnancy, is increasing in prevalence. Data regarding the cancer risk associated with GDM are sparse and limited to cancers of the breast and pancreas. This study was conducted to examine the risk of incident overall and site-specific malignancies associated with prior GDM in a historical cohort of women in a large health maintenance organization in Israel.

METHODS: All pregnant women aged 15-50 years who underwent 50-g glucose challenge tests between 13 March 1995 and 27 May 2009, without history of malignancy, diabetes, and infertility, were included. Clinical and demographic parameters at index date including age, socioeconomic level, BMI, and parity were collected. Diagnosis of gestational diabetes was based on the 100-g oral glucose tolerance test using Carpenter and Coustan criteria. Cancer diagnoses were obtained from the Israel Cancer Register through linkage data.

RESULTS: Among the 185,315 women who had undergone glucose challenge during the study period, 11,264 (6.1%) were diagnosed with GDM. During a total follow-up period of 1.05 million person-years (mean = 5.19 ± 3.9, median = 4.3), 2,034 incident cases of cancer were identified. GDM was associated with a hazard ratio (HR) of 7.06 (95% CI: 1.69-29.45) for pancreatic cancer (nine cases) and a HR of 1.70 (95% CI: 0.97-2.99) for hematological malignancies (177 cases). The association between GDM and hematological malignancies was limited to women with 5 or more years of follow-up (HR = 4.53; 95% CI: 1.81-11.31).

CONCLUSION: GDM is associated with an increased risk of pancreatic cancer and hematologic malignancies.

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Alcohol consumption during pregnancy among women in Israel

Senecky Y, Weiss N, ShalevSA, Peleg D, Dov Inbar, Chodick G, Shalev E, Bar-Hamburger R, Shuper A.
Journal of Population Therapeutics and Clinical Pharmacology [Formerly: Canadian Journal of Clinical Pharmacology] 2011;18:e261-e272
ABSTRACT
BACKGROUND:
Fetal alcohol spectrum disorder (FASD) is a range of disabilities caused by gestational exposure of the fetus to alcohol. Alcohol consumption in Israel has increased dramatically in the last decades. Our previous study revealed limited knowledge among Israeli medical professionals of the risks and potential long-term effects of FASD.

OBJECTIVES:
To evaluate the awareness and knowledge of women regarding the current recommendations on alcohol consumption during pregnancy, evaluate how many of the women received information regarding alcohol consumption during pregnancy from medical professionals, and their personal drinking habits during pregnancy.

METHODS:
A cross-sectional sample of new mothers in 3 large hospitals in Israel were asked to complete an ad hoc questionnaire on aspects of alcohol consumption during pregnancy.

RESULTS:
A total of 3815 women of mean age 30.4 years participated in the study; 82% were Jewish. Alcohol consumption during pregnancy was reported by 14.1%, including more than 17% of the Jewish women, 11.1% of the Christian women, and none of the Muslim women. Rates were higher among nonsecular and younger women and first-time mothers. 71.6% of the sample claimed that women should not drink alcohol at all during pregnancy, and 21.4% thought that it was permissible if limited to 2 drinks per week. Seventy-five percent had received no formal information from medical professionals regarding alcohol consumption during pregnancy.

CONCLUSIONS:
Alcohol consumption is frequent among pregnant women in Israel, especially young secular Jewish women with first pregnancies. Improved educational programs on the dangers of FASD are needed for both professionals and the general public.

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The rate of myocardial infarction events among patients with age-related macular degeneration: a population based study.

Golan S, Shalev V, Goldstein M, Treister, Loewenstein A, Chodick G.
Graefe's Archive for Clinical and Experimental Ophthalmology 2011;249:179-82
ABSTRACT
PURPOSE:
To examine the association between age-related macular degeneration (AMD) and the risk of myocardial infarctions (MIs) in a large health maintenance organization.

DESIGN:
A retrospective cohort study carried out at Maccabi Healthcare Services (MHS).

PARTICIPANTS:
A total of 6,546 patients aged ≥65 years who were diagnosed with AMD between April 18 1996 and June 6 2008, and 61,672 non-AMD patients frequency-matched for age and gender.

METHODS:
Participants were retrospectively followed to the day of leaving the MHS, to undergoing an MI, or to closure of the study on July 1 2008, whichever came earlier. The relative risk of MI associated with AMD was estimated using the Cox proportional hazard model.

MAIN OUTCOME MEASURES:
Incident myocardial infarction events.

RESULTS:
During the study period, there were 159 (5.1 per 1,000 person years [PY]) and 2,997 (4.2 per 1,000 PY) MIs respectively in the AMD and non-AMD patient groups. The age- and gender-adjusted hazard ratio (HR) of MI among AMD patients was 1.01 (95%CI: 0.85-1.20). Baseline medical characteristics associated with increased risk of mortality included diabetes mellitus, hypertension, older age, and male gender. The fully adjusted HR associated with AMD was 1.03 (95%CI: 0.87-1.22).

CONCLUSION:
Despite the shared risk factors associated with AMD and MIs, we found no increased risk of MI in AMD patients.

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Statin use and the Risk of Age Related Macular Degeneration in a Large Health Organization in Israel.

Shalev V, Sror M, Goldstein I, Chodick G.
Ophthalmic Epidemiol. 2011;18:83-90.
ABSTRACT
OBJECTIVE:
To investigate the association between persistent use of statins and the risk of age-related macular degeneration (AMD).

DESIGN:
A population-based retrospective cohort among adults who began statin therapy between 1998 and 2006 in a large health organization in Israel. The organization's central computerized databases were used to collect data on incident AMD cases diagnosed by ophthalmologists.

RESULTS:
A total of 108,973 individuals aged 55 or older were identified. During the study follow-up period 409,113 person-years, there were 2,732 incident AMD cases (6.68 per 1,000 person-years). The crude incidence density rate of AMD among patients at the lowest quintile of persistence with statins (7.18 per 1,000) was comparable to that of highest persistence quintile (7.13 per 1,000). After adjustment for potential confounders, patients in the highest quintile of persistence with statins had a hazard ratio of 0.99 (95% Confidence Interval: 0.78-1.26) for AMD compared with patients in the lowest proportion of days covered (PDC) quintile. In addition to age, AMD was found to associate with past smoking, asthma, diabetes and frequent visits to ophthalmologists or primary physicians prior to index date.

CONCLUSIONS:
Our study agrees with previous studies that showed no association between persistent use of statins and reduced risk of AMD. These results suggest that the early reports on a strong protective effect of statins against AMD development were probably a result of a small study effect.

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Type 2 Diabetes, Gestational Diabetes and the Risk of Cancer in Women: Epidemiologic Evidence and Possible Biologic Mechanisms.

Chodick G, Zucker I.
Womens Health (Lond Engl). 2011;7:227-37
ABSTRACT
At present, more than 10% of adult American women are diagnosed with diabetes mellitus (DM). As the prevalence of the disease increases, there is greater interest in the relationship between DM and other major health issues, such as cancer - one of the leading causes of death in the western world. This paper reviews the literature on the relationship between Type 2 DM and different types of cancer among women. We discuss the possible biological mechanisms that may link diabetes and cancer, important confounders, shared risk factors and a short review of the epidemiologic literature on the association between Type 2 DM and cancer of specific organs (pancreas, liver, colorectal, bladder, endometrial, non-Hodgkin's lymphoma and breast). We also examine the association between gestational diabetes, a closely related risk factor for DM in women, and subsequent risk of cancer. Cancer survival of diabetic women is also briefly discussed. The paper concludes with an agenda for future research targeting the relationship between diabetes and cancer.

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A retrospective study of the incidence of diagnosed Type 1 diabetes among children and adolescents in a large health organization in Israel, 2000-2008

Sella T, Shoshan A, Goren I, Shalev V, Blumenfeld O, Laron Z, Chodick G.
Diabetes Medicine. 2011 Jan; 28(1):48-53.
ABSTRACT
AIMS:
To determine the incidence and examine temporal trends of Type 1 diabetes among children aged < 18 years, in a large Israeli health organization.

METHODS:
All incident Type 1 diabetes cases diagnosed between 2000 and 2008 were ascertained from an automated diabetes registry based on members' electronic records and validated by comparison with the Israel Juvenile Diabetes Register.

RESULTS:
During the study period, a total of 648 incident cases of Type 1 diabetes were identified. The average annual age-and-sex-standardized incidence was 11.09 per 100,000 person-years. There was an annual 5.82% (95% CI 1.80-9.98%) rise in incidence, with a greater relative increase in toddlers under 5 years of age. Incidence increased with age and demonstrated seasonal variation. Mean age at onset of diabetes significantly (P = 0.07) decreased from 10.21 years (SD = 4.48) in 2000-2002 to 9.25 years (SD = 4.54) in 2006-2008. Among very young patients (< 5 years), average blood glucose values at diagnosis dropped from 32.4 mmol/l (SD = 9.5) to 19.5 mmol/l (SD = 11.0) over the study period, with little change in average glucose for older children.

CONCLUSIONS:
Incidence of diagnosed Type 1 diabetes continues to increase in Israel at a rate that is high compared with similar American and European populations. At the same time, the clinical presentation of children is changing.
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Diabetes, gestational diabetes and the risk of cancer in women: epidemiologic evidence and possible biologic mechanisms.

Chodick G, Zucker I.
Womens Health (Lond Engl). 2011 Mar;7(2):227-37
ABSTRACT
At present, more than 10% of adult American women are diagnosed with diabetes mellitus (DM). As the prevalence of the disease increases, there is greater interest in the relationship between DM and other major health issues, such as cancer - one of the leading causes of death in the western world. This paper reviews the literature on the relationship between Type 2 DM and different types of cancer among women. We discuss the possible biological mechanisms that may link diabetes and cancer, important confounders, shared risk factors and a short review of the epidemiologic literature on the association between Type 2 DM and cancer of specific organs (pancreas, liver, colorectal, bladder, endometrial, non-Hodgkin's lymphoma and breast). We also examine the association between gestational diabetes, a closely related risk factor for DM in women, and subsequent risk of cancer. Cancer survival of diabetic women is also briefly discussed. The paper concludes with an agenda for future research targeting the relationship between diabetes and cancer.

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Diabetes and Risk of Incident Cancer: A Large Population-Based Cohort Study in Israel .

Chodick G, Heymann AD, , Kokia E, Shalev V.
Cancer Causes Control, 2010; 21(6):879-87
ABSTRACT
Type 2 diabetes mellitus has been associated with an increased risk of a variety of cancers in observational studies, but few have reported the relationship between diabetes and cancer risk in men and women separately. The main goal of this retrospective cohort study was to evaluate the sex-specific risk of incident overall and site-specific cancer among people with DM compared with those without, who had no reported history of cancer at the start of the follow-up in January 2000. During an average of 8 years of follow-up (SD = 2.5), we documented 1,639 and 7,945 incident cases of cancer among 16,721 people with DM and 83,874 free of DM, respectively. In women, DM was associated with an adjusted hazard ratio of 1.96 (95% CI: 1.53-2.50) and 1.41 (95% CI: 1.20-1.66) for cancers of genital organs and digestive organs, respectively. A significantly reduced HR was observed for skin cancer (0.38; 95% CI: 0.22-0.66). In men with DM, there was no significant increase in overall risk of cancer. DM was related with a 47% reduction in the risk of prostate cancer. These findings suggest that the nature of the association between DM and cancer depends on sex and specific cancer site.
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Long-term trends in hepatitis A incidence following the inclusion of Hepatitis A vaccine in the routine nationwide immunization program

Chodick G, Heymann AD, Ashkenazi S, Kokia E, Shalev V.
Journal of Viral Hepatitis 2008; Sup2:62
ABSTRACT
For many years hepatitis A was one of the most common vaccine preventable diseases in Israel. In 1999, Israel became the first country to introduce an inactivated hepatitis A vaccine into its national childhood vaccination program. The objectives of the present study were to study trends in disease incidence after the implementation of the new vaccination policy and to assess vaccination coverage among children and adults in Israel. We used the databases of the second largest HMO in Israel (1.7 million members) to identify patients who had evidence of hepatitis A in 1998 and 2007 and to collect information on all subjects who received at least one dose of hepatitis A vaccine during the study period. Hepatitis A vaccination coverage in children <5 years and 5-14 years of age increased from 9% and 15% in 1998 to 89% and 68% in 2007, respectively. During this period the annual incidence of hepatitis A dropped from 142.4 per to 7.6 per 100 000. The most prominent reduction in the age-specific annual incidence rates was calculated in children <5 years from 239.4 per 100 000 in 1998 to 2.2 per 100 000 in 2007 and from 310.3 per 100 000 to 3.0 per 100 000 in children aged 5-14 years. In endemic areas, vaccination of infants and children against hepatitis A can greatly reduce the total burden of the disease.
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The shifting epidemiology of hepatitis A following routine childhood immunization program in Israel.

Chodick G, Green MS, Rosenmann L, Shalev V.
Preventive Medicine 2007; 45:386-91
ABSTRACT
OBJECTIVES:
In 1999 Israel became the first country to introduce immunization against hepatitis A to its national childhood vaccination program. The study objectives were to assess the uptake of hepatitis A vaccine following the new policy and to examine the incidence of hepatitis A and the number of prevented cases.

METHODS:
Data on incidence of hepatitis A and vaccination rates were obtained from a large health maintenance organization in Israel covering 1.6 million members. We identified all members that were diagnosed by a primary care physician as suffering from hepatitis A, had a positive hepatitis A virus-IgM test result, or were hospitalized due to hepatitis A between 1998 and 2004.

RESULTS:
The results indicate that 5 years following its inclusion in the national childhood immunization program, vaccination coverage levels with at least one dose of hepatitis A vaccine for children aged under 5 years and 5-14 years were 87% and 51%, respectively. During this period the annual incidence rates declined by 88% from 142.4 to 17.3 per 100,000. The most significant reduction in morbidity was observed among children.

CONCLUSIONS:
In endemic areas, vaccination of infants and children against hepatitis A may be efficient to greatly reduce the total burden of the disease.
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Seasonality in birth weight in Israel; New evidence suggests several global patterns.

Chodick G, Shalev V, Goren I, Inskip P
Annals of Epidemiology 2007;17:440-6
ABSTRACT
PURPOSE:
To investigate the effect of season on birth weight and whether it is expressed also in fluctuations of proportions of extreme birth weights.

METHODS:
Information about 225,545 singletons born during 1998 to 2004 was obtained from a large health maintenance organization in Israel. We conducted a linear regression analysis of the weight with month and year of birth, sex, maternal age, diabetes, and several meteorological factors as independent variables, which were also incorporated into multivariate logistic regression models to examine the effect of season of birth on the frequency of low birth weight (LBW, <2500 g) or macrosomia (>4000 g).

RESULTS:
A significant (P < .001) seasonal pattern in birth weights was observed, with a peak in July and a trough in January. Babies born in summer had an OR of 1.12 (95% CI; 1.07 to 1.18) for macrosomia compared with those born in the winter. No such pattern was found for LBW.

CONCLUSIONS:
While in regions of mid-latitude, summer is associated with relatively lower birth weight, possibly because of exposure to cold temperature during early or mid-pregnancy, our data suggest that in Israel, the peak birth weight is in summer, possibly because of increased exposure to sunlight in the last weeks of the pregnancy.
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Disease and Treatment-­Related Research

Adherence to treatment guidelines in Type 2 diabetes patients failing metformin monotherapy in a real-world setting

Tunceli K, Goldshtein I, Shengsheng Y, Sharon O, Brodovicz K, Gadir N, Katzeff H, Voss B, Radican L, Chodick G, Shalev V, Maor V, Karasik A.
Diabetes Management. 2015;5(1):17–24
ABSTRACT
Background
●● The importance of proactive diabetes treatment has been reinforced by recent diabetes guidelines. Understanding
the magnitude of clinical inertia in a real world cohort of patients with Type 2 diabetes mellitus, and understanding
the factors affecting intensity of care may improve diabetes care.
Results
●● Overall, 7705 patients were identified in a large computerized database of an Israeli HMO, in whom HbA1c
>7% was measured for the first time following at least 90 days on metformin therapy. Of these, 56% (n = 4336)
changed treatment within 1-year, by increasing metformin dose (36%), adding drugs (60%), or switching to other
medications (4%).
●● Strongest predictors of change were higher HbA1c, younger age and higher socioeconomic status (SES).
Conclusion
●● In this cohort, the extent of inertia appears to be smaller than that reported in previous studies. The may be due to intensive implementation of guidelines.
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Renal impairment among postmenopausal women with osteoporosis from a large health plan in Israel.

Jingbo Y, Goldshtein I, Shalev V, Chodick G, Ish-Shalom S, Sharon O, Modi A.
Arch Osteoporosis (2015) 10:8
ABSTRACT
Summary: Bisphosphonates are a first-line treatment for osteoporosis but require adequate renal function.We estimated the prevalence of renal impairment among osteoporotic women in Israeli. Approximately 2.3 % of women had renal impairment at a level that makes them inappropriate for bisphosphonate use, demonstrating the need for alternative therapies for osteoporosis treatment.

Purpose: The purpose of this study is to estimate the prevalence of renal impairment among postmenopausal osteoporotic women within a large Israeli health plan.

Methods: This was a retrospective analysis of Maccabi electronic medical records, including Israeli women aged ≥55with either an osteoporosis diagnosis or osteoporosis-related fracture between January 1, 2007, and December 31, 2011. The estimated glomerular filtration rate (eGFR), which was calculated from the lowest serum creatinine levels reported during the study period, was used to classify stage 1–5 renal impairment: normal ≥90, mild 60–89, moderate 30–59, severe 15–29, and failure <15mL/min/1.73m2, respectively. Outcomes were distributions
of renal impairment across the study population and stratified by age and osteoporosis-defining event.

Results: A total of 15,608 patients met all eligibility criteria. Patients with stage 1–5 renal function accounted for 25.2, 54.9, 18.5, 1.2, and 0.3 %, respectively, of all patients. Of osteoporotic patients, 2.3 % had eGFR levels (<35 mL/min/1.73 m2) that make them inappropriate for bisphosphonate use. This rate was 1.6 % among patients with an osteoporosis diagnosis and 3.8 % among patients with osteoporosis-related fracture. Within the group of renally impaired patients, older patients were overrepresented. Of the fracture group, patients with hip fractures had a higher prevalence of renal dysfunction (9.3%) than those having vertebral fractures (3.2 %) or other fractures (2.0 %).

Conclusions: Among postmenopausal women with osteoporosis, 2.3% had renal impairment which makes them inappropriate for bisphosphonate use in Israel.
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Adherence with statins and the risk of psoriasis: A population-based cohort study

Chodick G, Weitzman D, Shalev V, Weil C, Amital H.
British Journal of Dermatology 2015.
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No male predominance in offspring of women with rheumatoid arthritis or systemic lupus erythematosus.

Dar L, Shalev V, Weitzman D, Chodick G, Arnson Y, Amital H.
Immunologic Research 2014;60(2-3):361-5.
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.
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Multiple chronic disorders - health care system's modern challenge in the Maccabi Health Care System

Arbelle JE, Chodick G, Goldstein A, Porath A.
Israel Journal of Health Policy Research. 2014;29;3:29.
ABSTRACT
Background: One of the major challenges health care systems face in modern time is treating chronic disorders. In recent years, the increasing occurrence of multiple chronic disorders (MCC) in single individuals has compounded the complexity of health care. In 2008, it was estimated that worldwide as many as one quarter of the population between the ages of sixty five to sixty nine suffered from two or more chronic conditions and this prevalence rose with age. Clinical guidelines provide guidance for management of single disorders, but not for MCC. The aim of the present study was the study of the prevalence, distribution and impact of MCC in a large Israeli health system.

Methods: We performed a cross-sectional study of MCC in the Maccabi Healthcare System (MHS), Israel’s second largest healthcare service, providing care for approximately two million people. Data regarding chronic conditions was collected through electronic medical records and organizational records, as was demographic and socioeconomic data. Age and sex specific data were compared with previously published data from Scotland.

Results: Two thirds of the population had two or more chronic disorders. This is significantly higher than previously published rates. A correlation between patient age and number of chronic disorders was found, as was a correlation between number of chronic disorders and low socioeconomic status, with the exception of children due to a high prevalence of learning disabilities, asthma, and visual disturbances.

Discussion: MCC is very prevalent in the MHS population, increases with age, and except for children is more prevalent in lower socioeconomic classes, possibly due to the a combination of the structure of the Israeli universal insurance and requirements of the ministry of education for exemptions and benefits. A higher than previously reported prevalence of MCC may be due to the longtime use of use of integrated electronic medical records.

Conclusions: To effectively deal with MCC health care systems must devise strategies, including but not limited to, information technologies that enable shared teamwork based on clinical guidelines which address the problem of multiple, as opposed to single chronic disorders in patients.
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Gestational diabetes and the risk of cryptorchidism and hypospadias.

Trabert B, Chodick G, Shalev V, Sella T, Longnecker MP, McGlynn KA.
Epidemiology. 2014;25:152-3
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Long-term secular trends in the age at menarche in Israel: a systematic literature review and pooled analysis.

Flash-Luzzatti S, Weil C, Shalev V, Oron T, Chodick G.
Hormone Research in Pediatrics 2014;81:266-71.
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.
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Congenital hyperinsulinism, neonatal diabetes and the risk of malignancies: an international collaborative study. Preliminary communication.

Makov M, Chodick G, Mohnike K, Otonkoski T, Huopio H, Banerjee I, Cave H, Polak M, Christeansen HT, Hussain K, Deleon D, Stanley C, Cappa M, Ramos O,
Diabetic Medicine. 32, 701–703 (2015).
ABSTRACT
Growing evidence supports an association between diabetes or abnormal insulin signalling and cancer [1–4]; however, because of their rare occurrence, there is no established epidemiological evidence to support the relationship between neonatal diabetes and congenital hyperinsulinism and cancer occurrence.
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Old obstacles but new hopes: trying to understand the fibromyalgia construct.

Bar-On Y, Shalev V, Weitzman D, Chodick G, Amital H.
Israel Medicine Association Journal. 2014;16(10):625-6.
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Prevalence and factors associated with resistant hypertension in a large health maintenance organization in Israel.

Weitzman D, Chodick G, Shalev V, Grossman C, Grossman E.
Hypertension. In Press
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The Maccabi Glaucoma Study: prevalence and incidence of glaucoma in a large israeli health maintenance organization.

Levkovitch-Verbin H, Goldshtein I, Chodick G, Zigman N, Shalev V.
American Journal of Ophthalmology. In Press
ABSTRACT
PURPOSE:
To investigate the prevalence and incidence of glaucoma in a large health maintenance organization (HMO) in Israel.

DESIGN:
A population-based retrospective cohort study, conducted using electronic medical database.

METHODS:
Collected data included personal and medical characteristics.

SETTING:
Maccabi Healthcare Services, the second-largest HMO in Israel, insuring 2 million members and serving 25% of the population with a nationwide distribution.

STUDY POPULATION:
Maccabi members from January 2003 to December 2010.

MAIN OUTCOME MEASURES:
Prevalence and incidence of glaucoma according to the International Classification of Diseases, 9th revision, Clinical Modification diagnostic codes.

RESULTS:
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 6674 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<.01) higher in men in older ages.

CONCLUSIONS:
Glaucoma affects nearly 10% of the elderly population in Maccabi, with the highest risk of diagnosis at age 70-74. Since glaucoma leads to irreversible vision loss, the present estimates of morbidity should be of significant concern.
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Hemoglobin nonrecovery following acute myocardial infarction is a biomarker of poor outcome: a retrospective database study.

Leshem-Rubinow E, Steinvil A, Rogowski O, Zeltser D, Berliner S, Weitzman D, Raz R, Chodick G, Shalev V.
International Journal of Cardiology. 2013;20;169(5):349-53.
ABSTRACT
BACKGROUND:
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).

METHODS:
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 6 months 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.

RESULTS:
Last Hb measurement during a 6-24 month follow-up period was found to have the highest prognostic power. In males, Hb levels below 13 g/dL were gradually associated with a higher risk of events, reaching a HR of 4.13 at Hb levels <11 g/dL. In females, only Hb levels lower than 11 g/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.

CONCLUSIONS:
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.
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In-vitro fertilization cycles and outcomes in Maccabi Health Services, Israel, 2007-2010

Sella T, Segal Y, Goren I, Chodick G, Shalev V, Kol S.
Harefuah 2013;152:11-5, 60. Hebrew.
ABSTRACT
INTRODUCTION: 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.

OBJECTIVES: To describe IVF activity during the years 2007-2010 in Maccabi Healthcare Services, an independent health provider that reimburses IVF treatments.

METHODS: 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.

RESULTS: 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.

SUMMARY: 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.
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Prevalence of Epilepsy and Attention Deficit/Hyperactivity Disorder: A population-based study

Cohen R, Senecky Y, Inbar D, Chodick G, Shalev V, Shuper A, Raz R.
Journal of Child Neurology 2013;28:120-123
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Trends in gestational diabetes prevalence, diagnosis and risk factors in Israel: a large population based study

Sella T, Shalev V, Elchalal U, Chovel-Sella A, Chodick G.
The Journal of Maternal-Fetal & Neonatal Medicine 2013;26:412-6.
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Thrombosis following acute cytomegalovirus infection: a community prospective study.

Paran Y, Shalev V, Steinvil A, Justo D, Zimmerman O, Finn T, Berliner S, Zeltser D, Weitzman D, Raz R, Chodick G
Annals of Hematology 2013; 92:969-74.
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A case-crossover study of infectious diseases and new diagnosis of type 1 diabetes

Shoshan A, Sella T, Shohat T, Goren I, Shalev V, Chodick G.
Pediatric Diabetes. 2012;13(7):583-6.
ABSTRACT
Background
Infectious diseases have been associated with increased risk of type 1 diabetes (T1D). The objective of this case-crossover was to quantify the role of infectious diseases as triggers for T1D, 1 and 2 yr preceding disease diagnosis.

Methods
All children aged 2–18 yr diagnosed with T1D between 2004 and 2009 among a two million member Israeli healthcare organization were identified (n = 368). For each patient, visits to physicians with symptomatic infectious diseases during 1 and 2 yr before T1D diagnosis were collected and compared. A similar analysis was conducted in a population of non-diabetic members matched on exact date of birth, sex and socioeconomic status (n = 307).

Results
The rate of systemic viral infections was significantly higher in the year before T1D onset, as compared to the prior year [27 vs. 7%, respectively, odds ratio (OR) = 4.7, 95% confidence intervals (CI): 2.9–8.2]. This difference was most significant among patients diagnosed with T1D at the age of 2 to 6 (5 vs. 46%, respectively, OR = 27.0, 95% CI: 4.5–1105.4). Among non-T1D patients of the same age group, no difference was found in the proportion of patients with viral diseases 1 and 2 yr prior to T1D diagnosis (44 vs. 49%, respectively, OR = 0.8, 95% CI: 0.4–1.6). This unique association was limited only to viral diseases and to patients diagnosed with T1D at young age.

Conclusions
Our results indicate that T1D occurring in toddlers is characterized with a relatively low incidence of viral disease 2 yr prior to diagnosis and a much higher incidence in the subsequent year.
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Glucose-6-phosphate dehydrogenase deficiency and type 2 diabetes

Heymann AD, Cohen Y, Chodick G.
Diabetes Care. 2012;35(8):e58.
ABSTRACT
Glucose-6-phosphate dehydrogenase (G6PD) deficiency is a common X-linked human enzyme defect (1). There are a few reports that link G6PD deficiency to diabetes (2–4).

We undertook a cross-sectional study at Maccabi Healthcare Services, an Israeli HMO serving two million members. All interactions and information are captured on an electronic medical record. Our study population included all male members aged ≥25 years who were tested for G6PD between 2003 and 2010 and were found positive (a quantitative G6PD <7 U/g Hb). The testing was undertaken on a Trinity Olympus 2700 in the same central laboratory. All results from 2003 to 2010 were included. Patients with diabetes were drawn from our validated computerized registries (5). Our analysis was of the whole male Maccabi population stratified by age-group, presence in the diabetes register (yes/no), and G6PD deficiency (yes/no). The data were statistically analyzed by a standard statistical package (SPSS 15.0, Chicago, IL).

Among 940,085 individuals, 52,371 had G6PD deficiency. We found a significantly higher proportion of patients with G6PD deficiency among the diabetic population aged 45–64 years (P = 0.002; odds ratio 1.44 [95% CI: 1.145–1.815]) than would be expected by chance. We did not find a significant difference in HbA1c levels between the groups with and without G6PD deficiency.

These results showed a significantly increased association between prevalence of diabetes in the 45–65-year-old age-group among patients with G6PD deficiency when compared with the general population. This association may in fact be an underestimate in view of the fact that many individuals with G6PD deficiency in the general population have not undergone G6PD testing in our HMO or will have undergone testing before 2003 and therefore will have been misclassified. This study provides further evidence of a link between G6PD deficiency and diabetes.
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Performance of Pap smears among women in a large Israeli HMO during the years 2006 - 2008.

Raz R, Shavit O, Stein M, Cohen R, Schejter E, Chodick G, Shalev V.
Public Health 2012 In Press
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The long term risk of myelodysplastic syndromes among anemia patients: a population-based study.

Meytes D, Chodick G, Shalev V, Porath A
Leuk Res. 2012 Mar;36(3):327-30.
ABSTRACT
We have utilized the computerized data of a nationwide health plan to elucidate several epidemiologic aspects and risk factor of myelodysplastic syndromes (MDS) in Israel. The annual incidence rate (IR) of reported MDS was of 3.32 per 100,000. Among anemic patients aged 40+, the risk of reported MDS was 56.7 per 100,000. Only 44% of the reported MDS cases had an indication of bone marrow examination. In a multivariable model, older age, hemoglobin level <9 g/dl, white blood cell count of less than 3500/mm(3), and platelet count of less than 100×10(9)/L were associated with a significantly higher risk of MDS. The mean lag period from the first demonstration of anemia to the final diagnosis of MDS was 3.5 years. Our study results could be helpful for improving the detection of patients with high MDS risk, therapeutic decision-making, and designing interventional trials in the future.

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Epidemiology and comorbidity of severe mental illnesses in the community: findings from a computerized mental health registry in a large Israeli health organization.

Kodesh A, Goldshtein I, Gelkopf M, Goren I, Chodick G, Shalev V.
Soc Psychiatry Psychiatr Epidemiol. 2012 Feb 7.
ABSTRACT
PURPOSE: Maccabi Healthcare Services, a large health maintenance organization (HMO) operating in Israel, has recently constructed a computerized registry of patients with severe mental illnesses (SMI). In the present study, we aimed to use this registry to investigate the epidemiology of schizophrenia and bipolar affective disorder among adults, and to assess their comorbidity and mortality compared to the general population.

METHODS: In this historical cohort study, we investigated the age- and sex-specific prevalence and incidence rates of HMO members diagnosed with schizophrenia or bipolar affective disorder between 2003 and 2009. We compared their medical comorbidity and mortality to the general HMO population.

RESULTS: A total of 8,848 and 5,732 patients were diagnosed with bipolar (crude prevalence rate of 5 per 1,000) and schizophrenia (3 per 1,000), respectively. The annual incidence rates were 4.2 and 2.4 per 1,000 for schizophrenia and bipolar disorder, respectively. On average, schizophrenic men were diagnosed 4-5 years earlier than schizophrenic women. Compared to the general population, schizophrenia and bipolar disorder patients had a 12- and 9-year shorter life expectancy, respectively. They were also more likely to be diagnosed with diabetes mellitus (odds ratio of 1.9 and 1.6, respectively).

CONCLUSIONS: The current study demonstrates the potential use of automated medical databases to characterize the epidemiology of SMI in the community. The increased comorbidity and mortality among these patients has important implication for health authorities for prevention and delivery of health-care services.

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Prevalence of common thrombophilia and antiphospholipid antibodies in unexplained infertility women undergoing in vitro fertilization (IVF)

Steinvil A, Raz R, Berliner S, Steinberg DM, Zeltser D, Levran D, Shimron O, Sella T, Chodick G, Shalev V , Salomon O.
Thrombosis and Haemostasis 2012;108:1192-7
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The achievement of target cholesterol level differs between coronary heart disease and diabetic patients

Elis A, Chodick G, Heymann AD, Kokia E , Flash S, Lishner M, Shalev V
European Journal of Internal Medicine 2011; 22(3): 262-5
ABSTRACT
BACKGROUND:
Guidelines recommend that LDL-C level should be <100mg/dl among diabetes mellitus (DM) and coronary heart disease (CHD) patients.

OBJECTIVE:
To evaluate how patients with DM and CHD differ in attaining the target level and to examine the association between goal achievement, demographic and clinical parameters.

METHODS:
The study was conducted in Maccabi Healthcare Services, the second largest health maintenance organization in Israel. All patients with DM (n=54,261), CHD (n=24,083) or DM and CHD (n=15,370) who were listed in the computerized database and had at least one LDL-C level measurement between January 1, 2007 and July 15, 2008 were eligible. The percentage of patients who attained LDL-C level <100mg/dl and its association with demographic and clinical parameters were analyzed.

RESULTS:
The rate of reaching the LDL-C target level was higher among the CHD and CHD and DM patients than DM ones (67% vs. 57% vs. 50%, p<0.001, respectively). Male gender; 5th socioeconomic status quintile; underlying disease i.e. CHD, CHD and DM; high statins compliance; and revascularization by percutaneous coronary intervention predicted for reaching target level. DM; absence of renal function evaluation; hospitalizations; HbA1C>7% or missing its measurements had a negative predictive value.

CONCLUSIONS:
The rate of reaching LDL-C target level should be increased in all high risk patients, mainly diabetic ones. Efforts should include educational programs to physicians and patients regarding the importance, the need to adhere and to intensify the cholesterol lowering treatment.

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Variations in hemoglobin before colorectal cancer diagnosis.

Goldshtein I, Neeman U, Chodick G, Shalev V.
European Journal of Cancer Prevention 2010;19:342-344.
ABSTRACT
We have conducted the present case-control study to examine whether long-term variations in blood hemoglobin (Hb) levels within the normal range could detect subtle gastrointestinal bleeding in the early development of colorectal cancer (CRC). A total of 1074 CRC cases aged 45-75 years that have been diagnosed with CRC and had normal Hb levels were frequency matched for age and sex with cancer-free individuals at a ratio of 10 controls per case. Our retrospective analysis indicates that starting from 4 years prior to cancer diagnosis, a progressive significant (P<0.001) decrement in Hb levels (0.28 g/dl per 6 months) was found among cases but not among controls. CRC patients were characterized in an on-going, long-term, logarithmic decrement in Hb levels. Such small changes within the normal Hb range could be missed by health providers, but automatically detected by computerized alert algorithms.
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The uptake of rotavirus vaccine and its effectiveness in preventing acute gastroenteritis in the community.

Muhsen K, Chodick G, Goren S, ShalevV, CohenD
Vaccine 2010;29:91-94
ABSTRACT
We examined the uptake of rotavirus vaccine and its effectiveness in preventing acute gastroenteritis (AGE) in the community. Data on rotavirus vaccines purchases and AGE were extracted from the computerized database of a large health maintenance organization in Israel. The incidence of AGE requiring a physician visit during 2008-09 rotavirus season among vaccinated and non-vaccinated children were compared, and vaccine effectiveness was calculated as: (1-Relative Risk)×100. During the study period, the uptake of rotavirus vaccine (mostly monovalent) reached 55.1% (N=19,108) of the studied cohort. The risk of AGE requiring a physician visit was 23.2% and 46.4% among vaccinated and unvaccinated children, respectively, yielding an effectiveness of 50.1% (95% CI: 47.5%, 52.6%). Rotavirus monovalent vaccine was highly effective in preventing AGE in the community.

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Effectiveness of rotavirus vaccines against rotavirus gastroenteritis associated with hospitalizations in Israel- A case-control study.

Muhsen K, Shulman L, Kasem E, Rubinstein U, Shecter J, Kremer A, Goren S, Zilberstein I, Chodick G, Ephros M, Cohen D.
Human Vaccines 2010; 6: 450-454
ABSTRACT
The association between rotavirus gastroenteritis (RVGE)-associated hospitalization and rotavirus vaccine receipt was examined, and vaccine effectiveness was estimated in a case-control study conducted between 11/2007 and 12/2009 among Israeli children age eligible for rotavirus vaccination. Cases (n=111) were hospitalized children with diarrhea testing positive for rotavirus by immunochromatography. Controls (n=216) were hospitalized children with diarrhea testing negative for rotavirus. Among controls 36 (16.7%) children were vaccinated against rotavirus compared with two children (1.8%) among cases (p < 0.001). Rotavirus immunization was associated with lower risk of RVGE-associated hospitalization; adjusted OR 0.106 (95% CI 0.024, 0.481), yielding a vaccine effectiveness of 89.4% (95% CI 51.9%, 97.6%) in preventing hospitalization. These data demonstrate high effectiveness of rotavirus vaccines in a high income country
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Use of hormone replacement therapy, 1998-2007: sustained impact of the Women's Health Initiative findings.

Silverman BG, Kokia ES
Annals of Pharmacotherapy 2009 Feb;43(2):251-8
ABSTRACT
BACKGROUND:
Trials of hormone replacement therapy (HRT) for prevention of chronic disease in postmenopausal women have suggested that the risks of treatment outweigh the benefits. The publication in 2002 of the Women's Health Initiative (WHI) study sparked a rapid decline in HRT purchases among American women.

OBJECTIVE:
To examine the impact of the WHI findings on patterns of HRT use in Israeli women.

METHODS:
We linked purchases of estrogen preparations from 1998 to 2007 by female Israeli health maintenance organization members aged 45 years and older to membership data. For each year, we calculated total annual purchases and rate of HRT utilization, characterized new users by age and mode of therapy, and examined rates of switching between modes of therapy.

RESULTS:
Twenty percent of women aged 45 years and older purchased estrogen products in 2001, versus 10% in 2007 (p < 0.001; chi(2)). Vaginally administered products accounted for a rising percentage of purchases, from 5% in 1999 to 18% in 2007. An increasing percentage of new users aged 55 years and older started with a vaginal product (62% in 1999, 82% in 2007). After 2002, new users of oral therapy discontinued use more quickly than those who started oral therapy before 2002. Tibolone accounted for an increasing percentage of oral drugs purchased (12% in 2003, 29% in 2007).

CONCLUSIONS:
The WHI findings had a rapid and sustained impact on HRT utilization in a large population of Israeli women, including a sharp decrease in the rate of use, particularly of oral preparations, as well as reduced duration of therapy and increased use of vaginal preparations and tibolone as first choices for treatment.

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The association between glycemic, lipids and blood pressure control among Israeli diabetic patients

Elis A, Rosenmann L, Chodick G, Heymann AD, Kokia E, Shalev V
QJM 2008; 101:275-­80
ABSTRACT
BACKGROUND:
It is recommended that in diabetes mellitus patients all risk factors for cardiovascular disease should be controlled.

AIM:
To evaluate the rate of reaching all glycemic, lipids and blood pressure target levels among diabetic patients in Israel and to analyze demographic and clinical parameters associated with it.

DESIGN: A cross-sectional study.

METHODS:
The study was conducted in Maccabi Healthcare Services, Israel's second largest health maintenance organization. All patients (n = 41 936), older than 20 years, who were listed on Maccabi Healthcare Service's diabetes mellitus computerized database and had all three study parameters (HbA1c, LDL-C and blood pressure levels during 2005) were eligible for the study. The rate of reaching HbA1c <7.0%, LDL-C <100 mg/dl and blood pressure <130/85 mmHg, as well as its association with various demographic and clinical parameters were analyzed.

RESULTS:
Only 13% of all study patients achieved all three target levels. The parameters which were significantly associated with goal achievement were compliance to medical treatment for all three parameters (OR 1.56, 95% CI 1.44-1.69, P = 0.0001), male gender (OR 1.42, 95% CI 1.31-1.54, P = 0.0001), comorbidity with ischemic heart disease (OR 1.23, 95% CI 1.13-1.34, P = 0.0001), and >12 visits per year to family physician (OR 1.10, 95% CI 1.02-1.19, P = 0.012).

CONCLUSION:
Non-compliance with treatment and sub-optimal follow-up by family physicians are associated with increased risk of failure to control major risk factor among diabetic patients.
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In a population-­based cohort of diabetes patients, men and women had similar risks for all-­cause mortality

Shalev V, Chodick G, Bialik M, Green MS, Heymann AD
Journal of Clinical Epidemiology 2007; 60:86-­93
ABSTRACT
OBJECTIVES:
To compare death rates of diabetic men and women relative to the general population and to identify sex-specific risk factors for all-cause mortality.

STUDY DESIGN AND SETTINGS:
In the current historical prospective cohort study, standardized mortality ratios (SMRs) were calculated for 19,657 men and women with diabetes in a large Israeli health care organization compared to the mortality in the general population from 1999 to 2003. In addition, sex-specific survival analyses were performed for men and women separately using baseline data obtained between 1995 and 1999.

RESULTS:
During the study follow-up (90,899 person-years), 2,924 deaths were identified. The SMR for diabetic women (1.40; 95% confidence interval [CI]: 1.33, 1.47) was significantly (P<0.01) higher than for diabetic men (1.20; 95% CI: 1.14, 1.26). Age, glycated hemoglobin, serum creatinine, low-density lipoprotein, high-density lipoprotein, dialysis, use of angiotensin-converting enzyme inhibitors, and insulin were similarly associated with mortality in both sexes. Residing in the south of Israel was related with higher risk among men but with decreased risk among women.

CONCLUSIONS:
The study indicates that diabetes seems to eliminate the relative protection against death usually seen in women. It also suggests that most risk factors are comparable between the sexes, underlining the importance of similarly intensive disease management in diabetic women and in diabetic men.
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The association between Psoriasis, Diabetes Mellitus and Atherosclerosis in Israel

Shapiro J, Cohen AD, David M, Chodik G, Viner A, Kremer E, Heymann AD
Journal of the American Academy of Dermatology 2007;56:629-­34
ABSTRACT
BACKGROUND:
Previous reports demonstrated an association between psoriasis and other diseases including heart failure and diabetes mellitus.

OBJECTIVES:
Our aim was to describe the association between psoriasis, diabetes mellitus, and atherosclerosis in Israel.

METHODS:
A cross-sectional study was performed utilizing the database of Maccabi Healthcare Services (MHS), a large health provider organization in Israel. Case patients were defined as subjects who were diagnosed with psoriasis. Patients with diabetes and atherosclerosis were identified by using the MHS diabetes and cardiovascular registries, respectively. The control group included MHS enrollees without psoriasis. The proportion of diabetes and atherosclerosis among case and control groups was compared. Chi-square tests were used to compare categorical parameters. Logistic regression models were used for multivariate analyses.

RESULTS:
The study included 46,095 patients with psoriasis (case patients) and 1,579,037 subjects without psoriasis (control patients). The age-adjusted proportion of diabetes was significantly higher in psoriasis patients as compared with the control group (odds ratio [OR] 1.27, 95% confidence interval [CI] 1.1-1.48). The age-adjusted proportion of atherosclerosis was significantly higher in psoriasis patients as compared with the control group (OR 1.28, 95% CI 1.04-1.59). In patients with psoriasis, a multivariate logistic regression model demonstrated an association between diabetes and the multiple use of very potent topical steroids (P < .05) or use of systemic medication for psoriasis (methotrexate, cyclosporine or acitretin) (P < .001). A similar model demonstrated an association between atherosclerosis and the use of phototherapy (P < .001).

LIMITATIONS:
Our study was based on a computerized database. The diagnosis of psoriasis was based on digitally transmitted data. Therefore overestimation (false-positive cases) and underestimation (false-negative cases) of psoriasis patients may exist, thereby being a source for information bias. A second limitation is selection bias that may occur due to the possibility that reporting of both psoriasis and associated illnesses is higher in individuals who are seeking medical care. A third limitation concerns the causal effect between occurrence of psoriasis and atherosclerosis or diabetes. The dataset of MHS records diagnoses only from 1997 and does not record the date of disease onset.

CONCLUSIONS:
Our study supports previous reports for an association between psoriasis and atherosclerosis and psoriasis and diabetes. Further study is needed to support this observation.
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Elevated 13C urea breath test values females infected with Helicobacter pylori

Shmuely H, Yahav J, Samra Z, Chodick G, Ofek I
Digestive Diseases and Sciences. 2007;52:402-­4
ABSTRACT
(13)C-urea breath test (UBT) for the diagnosis of Helicobacter pylori requires a high density and active bacteria and has the potential to provide a noninvasive index of bacterial growth. We describe the gender differences in delta over baseline (13)C-UBT values in 7373 patients (4531 females and 2842 males) who underwent (13)C-UBT test for the diagnosis of H. pylori infection. A significantly (P<.001) higher mean +/- SD excess delta (13)CO(2) excretion was recorded in females (24.7+/-17.4) compared to males (17.6+/-11.8) aged 10-80 years. The age-adjusted difference between sexes was 7.1 (95% confidence interval, 6.4-7.9). Our analysis demonstrates quantitatively for the first time gender associated differences in H. pylori host interaction. This study suggests that infected females have a higher bacterial load and therefore may potentially infect their children at a higher degree than males.
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The epidemiology of diabetes in a large Israeli HMO

Chodick G, Heymann AD, Shalev V, Kookia E
European Journal of Epidemiology 2003;18:1143-­1146
ABSTRACT
Diabetes is one of the most prevalent non-communicable disease globally and it is one of the leading cause for death in most developed countries. The current population-based study aim was to describe to the epidemiology of diabetes in Israel by using our HMO's automated medical databases. All diabetic patients appearing in the diabetes registry among 1.6 million insured members in the second largest HMO in Israel were selected for epidemiological analysis. We identified 39,768 diabetic patients (crude prevalence rate of 2.6%). Higher age-specific prevalence rates were recorded among males. The highest age-specific prevalence rate of diabetes was calculated for men aged 75 and above (18.1%). A rise in the prevalence and mortality rates was recorded between 1999 and 2001 female (from 1.9 to 2.8 per 100,000) and for men (from 2.3 to 3.8 per 100,000). The current study demonstrates the potential of using large automated medical and administrative databases to determine the epidemiology of chronic disease, such as diabetes. The rise in the prevalence and mortality of diabetes patients has important implication for Israeli health authorities and should be seriously regarded.
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Burden of Disease and Cost-­Effectiveness Studies

Multiple chronic disorders - health care system's modern challenge in the Maccabi Health Care System

Arbelle JE, Chodick G, Goldstein A, Porath A.
Israel Journal of Health Policy Research. 2014;29;3:29.
ABSTRACT
Background: One of the major challenges health care systems face in modern time is treating chronic disorders. In recent years, the increasing occurrence of multiple chronic disorders (MCC) in single individuals has compounded the complexity of health care. In 2008, it was estimated that worldwide as many as one quarter of the population between the ages of sixty five to sixty nine suffered from two or more chronic conditions and this prevalence rose with age. Clinical guidelines provide guidance for management of single disorders, but not for MCC. The aim of the present study was the study of the prevalence, distribution and impact of MCC in a large Israeli health system.

Methods: We performed a cross-sectional study of MCC in the Maccabi Healthcare System (MHS), Israel’s second largest healthcare service, providing care for approximately two million people. Data regarding chronic conditions was collected through electronic medical records and organizational records, as was demographic and socioeconomic data. Age and sex specific data were compared with previously published data from Scotland.

Results: Two thirds of the population had two or more chronic disorders. This is significantly higher than previously published rates. A correlation between patient age and number of chronic disorders was found, as was a correlation between number of chronic disorders and low socioeconomic status, with the exception of children due to a high prevalence of learning disabilities, asthma, and visual disturbances.

Discussion: MCC is very prevalent in the MHS population, increases with age, and except for children is more prevalent in lower socioeconomic classes, possibly due to the a combination of the structure of the Israeli universal insurance and requirements of the ministry of education for exemptions and benefits. A higher than previously reported prevalence of MCC may be due to the longtime use of use of integrated electronic medical records.

Conclusions: To effectively deal with MCC health care systems must devise strategies, including but not limited to, information technologies that enable shared teamwork based on clinical guidelines which address the problem of multiple, as opposed to single chronic disorders in patients.
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Determinants of cost-related non-adherence to medications among chronic patients in Maccabi healthcare services, Israel.

Simon-Tuval, Triki N, Chodick G, Greenberg D.
Value in Health In Press
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A Survey of Out-of-Pocket Costs for Children with Autism Spectrum Disorder in Israel

Raz R, Lerner L, Shalev V, Chodick G, Gabis L.
Journal of Autism and Developmental Disorders 2013;43: 2295-302
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A population based study of the epidemiology of Herpes Zoster and its complications.

Weitzman D, Shavit O, Stein M, Cohen R, Chodick G, Shalev V.
Journal of Infection 2013;67:463-9
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The Maccabi Glaucoma Study: prevalence and incidence of glaucoma in a large israeli health maintenance organization.

Levkovitch-Verbin H, Goldshtein I, Chodick G, Zigman N, Shalev V.
American Journal of Ophthalmology. In Press
ABSTRACT
PURPOSE:
To investigate the prevalence and incidence of glaucoma in a large health maintenance organization (HMO) in Israel.

DESIGN:
A population-based retrospective cohort study, conducted using electronic medical database.

METHODS:
Collected data included personal and medical characteristics.

SETTING:
Maccabi Healthcare Services, the second-largest HMO in Israel, insuring 2 million members and serving 25% of the population with a nationwide distribution.

STUDY POPULATION:
Maccabi members from January 2003 to December 2010.

MAIN OUTCOME MEASURES:
Prevalence and incidence of glaucoma according to the International Classification of Diseases, 9th revision, Clinical Modification diagnostic codes.

RESULTS:
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 6674 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<.01) higher in men in older ages.

CONCLUSIONS:
Glaucoma affects nearly 10% of the elderly population in Maccabi, with the highest risk of diagnosis at age 70-74. Since glaucoma leads to irreversible vision loss, the present estimates of morbidity should be of significant concern.
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The Direct Medical Cost of Cardiovascular Diseases, Hypertension,   Diabetes, Cancer, Pregnancy and Female Infertility in a Large HMO in Israel

Chodick G, Porath A, Alapi H, Sella T, Flash S, Wood F, Shalev V
Health Policy 2010;95:271-6
ABSTRACT
OBJECTIVES:
The aim of this study was to assess the direct medical cost of treating major chronic illnesses in Maccabi Healthcare Services, a 1.8 million member health maintenance organization in Israel.

METHODS:
Direct medical costs were calculated for each member in 2006. We used multiple linear regression models to evaluate the overall costs of chronic conditions (cardiovascular diseases, diabetes mellitus, hypertension, female infertility treatments, and cancer), pregnancy and treatments for female infertility.

RESULTS:
According to the study model, hypertension was associated with the largest direct medical costs in both sexes. Cardiovascular diseases accounted for 9.5% of the total direct medical costs in men, but only 5.9% in women. Diabetes mellitus accounted for 3.5% of the total medical costs both in men and women and is comparable to the total pregnancy-related costs in women.

CONCLUSIONS:
The findings indicate that hypertension, diabetes mellitus and female infertility treatments impose a considerable economic burden on public healthcare services in Israel which is comparable with the costs of cancer and cardiovascular diseases.
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Potential impact and cost-­effectiveness analysis of rotavirus vaccination of children in Israel

Chodick G, Waisbourd-­Zinman O, Shalev V, Kokia E, Rabinovich M, Ashkenazi S
European Journal of Public Health 2009;19 :254-­9.  
ABSTRACT
BACKGROUND:
Rotavirus is a common cause of acute gastroenteritis in children under 5 years of age. Two effective vaccines against rotavirus gastroenteritis were recently licensed in many countries throughout the world. The study aimed to investigate the cost effectiveness of vaccinating an Israeli birth cohort of 143 500 children.

METHODS:
The cost-effectiveness analysis was determined using a decision analytical model, based on evidence-based estimates of the medical burden of rotavirus gastroenteritis in Israel.

RESULTS:
According to our model, a routine rotavirus immunization program using Rotarix and RotaTeq would prevent 17,801 and 13,288 office visits and 645 and 535 hospitalizations every year, respectively. When direct healthcare costs and societal costs are taken into account, the incremental cost-effectiveness ratio per gained QALY for Rotarix and RotaTeq are $10,995 and $30,674, respectively.

CONCLUSION:
Rotavirus vaccination can be considered a cost-effective intervention in Israel, depending on the precise vaccine price.
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Cost-­effectiveness of varicella vaccination of healthcare workers

Chodick G, Ashkenazi S, Livni G, Lerman Y
Vaccine 2005; 23:5064-­5072  
ABSTRACT
OBJECTIVE:
Although transmission of VZV is recognized as an important cause for morbidity in health care workers (HCWs), there is no general agreement on the recommended immunization policy. This study aimed to evaluate several of such prevention policies in economic terms.

SETTINGS:
Analysis of the cost per avoided future varicella cases among HCWs in Israel.

METHODS:
A cost-effectiveness analysis was performed by comparing the cost per avoided case of varicella among a theoretical cohort of 63,353 physician and nurses aged less than 45 years in Israel. Four policies were examined: (a) do nothing (status quo); (b) vaccination of susceptible workers using VZV serotesting; with (c) or without anamnestic history of chickenpox; and (d) presumptive mass vaccination of all eligible workers. A Markov-based model was developed using data from our recent seroepidemiological study in target population and from the literature.

RESULTS:
Screening and vaccination of susceptible workers using anamnestic selection is expected to reduce future cases, within 20 years since vaccination, from 58.3 to 33.0 with an incremental cost of 23,713 US dollars per avoided cases. Using only serological tests to detect susceptible workers would prevent additional 5.7 cases with an incremental cost of 206,692 US dollars per avoided case. Vaccinating all HCWs without serotesting, raises the costs markedly, with almost identical effectiveness, resulting in an incremental cost of 10.4 million US dollars per avoided case. Sensitivity analyses do not alter the ranking of the options.

CONCLUSION:
From the employer's perspective, routine varicella vaccination program for HCWs with or without selection of susceptible workers is extremely expensive compared to other high-cost practiced approaches. Substantial reduction in cost of vaccination may alter this conclusion.
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The direct medical cost of diabetes in Israel

Chodick G, Heymann AD, Wood F, Kokia E
European Journal of Health Economics 2005;6:166-­171
ABSTRACT
Diabetes mellitus is an important chronic disease with a growing prevalence that absorbs an ever increasing investment of resources. This population-based study evaluated the direct medical costs of diabetes mellitus in an HMO setting. We evaluated both the total cost of diabetic patients and their added cost in comparison to other HMO members (diabetes-related costs). Data were obtained for the years 1999-2001 in a cohort of 24,632 diabetic patients followed up for 3 years drawn from the computerized medical administrative database of a large HMO in Israel, insuring around 25% of the population. The mean direct cost of the medical treatment of a diabetic patient rose 29% from US $2,017 in 1999 to $2,601 in 2001 (in 2001 terms) in comparison to a 19.7% rise (from $1,246 to $1,492). Hospitalizations, medication, and physician visits account for 39%, 29%, and 21% of the total diabetic patient costs, respectively. Dialysis, insulin intake, impaired creatinine, and elevated HbA1c were associated with increased expenditures. According to our results, the total national medical cost of diabetes alone in 2001 was $317 million and that of diabetic patients was $564 million, 6.9% and 12.4% of the total Israeli HMO budget, respectively. The study presents the use of a population-based computerized database to comprehensively assess the economic burden of disease and the potential savings from prevention. The study data suggest a rise in the cost of diabetes which has implications for prevention and treatment policies.
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Pharmacoepidemiology

Seasonal influenza vaccination rates and reasons for non-vaccination in children with gastrointestinal disorders

Peleg N, Zevit N, Shamir R, Chodick G, Levy I.
Vaccine. 2015; 1;33(1):182-6.
ABSTRACT
Objectives

Despite advances in the treatment and prevention of influenza, it is still considered an important cause of morbidity and mortality worldwide. Annual vaccination is the safest and most effective mean of prevention. Our study aims were to explore the uptake of influenza vaccination among children with gastrointestinal disorders, and to characterize non-adherent patients.

Methods

The present cross-sectional study included parents of pediatric patients attending the Gastroenterology Institute at Schneider Children's Medical Center of Israel between September and October 2011. Parents were asked to complete a questionnaire concerning demographic and clinical parameters, influenza vaccination of the child, and reasons for not vaccinating the child, when appropriate.

Results

The study population included 273 patients (50% female), with a median age of 10 years (range, 2–18 years). Overall, the rate of seasonal influenza vaccination was 30.8%. Higher rates were found among immunosuppressed patients (46.1%), and in patients with inflammatory bowel disease (50%). There was no significant effect of patient age, gender, ethnic origin or parental level of education on the vaccination rate. Vaccination rates were significantly associated with parents’ information and knowledge of, as well as their personal beliefs regarding the vaccine (P < 0.001).

Conclusions

Influenza vaccination rates are relatively low in the pediatric population attending gastroenterology clinics, in both high- and low-risk groups. The importance of parental knowledge in compliance with influenza vaccination of children should prompt general pediatricians and gastroenterologists to discuss and address the common misconceptions regarding the vaccine.
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Association between persistence with statin therapy and reduction in low-density lipoprotein cholesterol level: analysis of real-life data from community settings.

Shalev V, Goldshtein I, Halpern Y, Chodick G.
Pharmacotherapy. 2014;34(1):1-8.
ABSTRACT
Study Objectives:
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.

Design:
Retrospective, population-based cohort study.

Data Source:
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.

Patients:
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.

Measurements and Main Results:
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.

Conclusions:
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.
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Trends in statin therapy initiation during the period 2000-2010 in Israel.

Shalev V, Weil C, Raz R, Goldshtein I, Weitzman D, Chodick G.
European Journal of Clinical Pharmacology In Press
ABSTRACT
PURPOSE:
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.

METHODS:
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.

RESULTS:
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.

CONCLUSIONS:
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.
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Rates of adherence and persistence with allopurinol therapy among gout patients in Israel

Zandman-Goddard G, Amital H, Shamrayevsky N, Raz R . Shalev V , Chodick G.
Rheumatology (Oxford) Rheumatology (Oxford). 2013;52:1126-31.
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.
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Continuation of statin therapy and primary prevention of nonfatal cardiovascular events.

Shalev V, Goldstein I, Porath A, Weitzman D, Shemer J, Chodick G.
American Journal of Cardiology 2012;110:1779-86.
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ACE Inhibitors Initiation is associated with Hemoglobin Reduction among Patients without Renal Failure

Leshem-Rubinow E, Steinvil A, zeltser D, Berliner S, Rogowski O, Raz R, Chodick G, Shalev V.
Mayo Clinic Proceedings 2012;87:1189-95
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Serotonin Reuptake Inhibitors and the risk for fractures and bone loss: a population based cohort study.

Zucker I, Chodick G, Grunhausd L, Raz R, Shalev V.
CNS Drugs 2012 in press
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Use of Hormone Replacement Therapy, 1998–2007: Sustained Impact of the Women’s Health Initiative Findings

Silverman, B, Kokia, E.
Annals of Pharmacotherapy 2009 Feb;43(2):251-8
ABSTRACT
BACKGROUND:
Trials of hormone replacement therapy (HRT) for prevention of chronic disease in postmenopausal women have suggested that the risks of treatment outweigh the benefits. The publication in 2002 of the Women's Health Initiative (WHI) study sparked a rapid decline in HRT purchases among American women.

OBJECTIVE:
To examine the impact of the WHI findings on patterns of HRT use in Israeli women.

METHODS:
We linked purchases of estrogen preparations from 1998 to 2007 by female Israeli health maintenance organization members aged 45 years and older to membership data. For each year, we calculated total annual purchases and rate of HRT utilization, characterized new users by age and mode of therapy, and examined rates of switching between modes of therapy.

RESULTS:
Twenty percent of women aged 45 years and older purchased estrogen products in 2001, versus 10% in 2007 (p < 0.001; chi(2)). Vaginally administered products accounted for a rising percentage of purchases, from 5% in 1999 to 18% in 2007. An increasing percentage of new users aged 55 years and older started with a vaginal product (62% in 1999, 82% in 2007). After 2002, new users of oral therapy discontinued use more quickly than those who started oral therapy before 2002. Tibolone accounted for an increasing percentage of oral drugs purchased (12% in 2003, 29% in 2007).

CONCLUSIONS:
The WHI findings had a rapid and sustained impact on HRT utilization in a large population of Israeli women, including a sharp decrease in the rate of use, particularly of oral preparations, as well as reduced duration of therapy and increased use of vaginal preparations and tibolone as first choices for treatment.
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Long-Term Persistence with Statin Therapy in a Non-For-Profit Health Maintenance Organization: A Population-Based Retrospective Cohort Study

Chodick G, Shalev V, Gerber Y, Heymann AD, Silber H, Simah V, Kokia E.
Clinical Therapeutics 2008;30:2167-2179
ABSTRACT
BACKGROUND:
Although discontinuing lipid-lowering treatment can cause preventable morbidity, previously published reports have indicated considerable variability in persistence with statin use. In general, such reports have been limited by short follow-up periods and modest study populations.

OBJECTIVES:
The aims of this study were to assess long-term persistence with statins and to identify the sociodemographic, clinical, and pharmacotherapy-related factors associated with long-term persistence with statin treatment in first-time users in Israel.

METHODS:
This retrospective cohort study used data from adult enrollees of a not-for-profit health maintenance organization and from death certificates in Israel. Eligible patients initiated statin treatment between 1998 and 2006. Persistence was assessed separately in patients with no indication of a cardiovascular disease (primary prevention) or coronary artery disease (secondary prevention). Treatment persistence and proportion of days covered (PDC) were measured using the interval between the date of the first prescription dispensation (index date) and the point of discontinuation.

RESULTS:
Data from 229,918 patients were included (primary prevention, 136,052; secondary prevention, 93,866). The PDC was significantly higher in the secondary-prevention group compared with the primary-prevention group (59% vs 45%; P < 0.001). In both cohorts, persistence continually diminished from the index date through follow-up, with > or = 75% of patients discontinuing statin therapy by 2 years. Baseline predictors of discontinuation of statin treatment included younger age, female sex, lower socioeconomic status (SES), absence of diabetes or hypertension, no concurrent use of beta-blockers or angiotensin-converting enzyme inhibitors, and less health service utilization. New immigrants and patients in the primary-prevention group who had a baseline low-density lipoprotein cholesterol concentration <130 mg/dL were at increased risk for treatment discontinuation.

CONCLUSION:
In this study in these patients receiving first-time statin treatment in Israel, we found poor persistence with statins among both the primary- and secondary-prevention cohorts, especially among new immigrants and patients with low SES despite low out-of-pocket prescription costs and free access to health services.
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Brand Versus Generic Alendronate: Gastrointestinal Effects Measured by Resource Utilization

Halkin, H, Dushenat, M, Silverman, B, Shalev, V, Loebstein, R, Lominicky, Y, Friedman, N.
Annals of Pharmacotherapy 2007 Jan;41(1):29-34
ABSTRACT
BACKGROUND:
Adverse reactions related to the upper gastrointestinal tract (UGIT) that are associated with generic alendronate formulations may differ from those associated with the brand drug.

OBJECTIVE:
To test the hypothesis that adverse UGIT effects of alendronate formulations may differ between generic and brand products.

METHODS:
We conducted a database health resource utilization analysis of UGIT outcomes in patients who started treatment with generic or brand alendronate formulations during 2001-2005. We included 6962 patients who were treated continuously for 3 months with 1 of 4 alendronate formulations: brand 10 mg/day (Merck, Sharpe & Dohme, n = 1418), generic A 10 mg/day (Teva, Israel, n = 650), generic B 10 mg/day (Unipharm, Israel, n = 628), and brand 70 mg/wk (n = 4266). In these patients, who had neither filled a prescription for alendronate nor had any gastrointestinal problems in the year preceding the study, we compared incidence rates of new use of gastric medications (H2-blockers, proton-pump inhibitors, or antacids), gastroenterology visits, endoscopies, and hospital admissions.

RESULTS:
Incident rate ratios (IRR) for treatment discontinuation were higher with both daily generic products (IRR 1.3; 95% CI 1.04 to 1.63). Adherence (medication possession ratio [MPR] >80%) was better with brand 10 mg/day (IRR 1.19; 95% CI 1.11 to 1.27). All comparisons were adjusted for use of concurrent corticosteroids, nonsteroidal antiinflammatory drugs, and potassium supplements. Hospitalization rates (2.7-3.2%) were similar in all groups. New use of gastric medications (3.4-4.9%) was lower with brand 10 mg/day (IRR 0.71; 95% CI 0.53 to 0.95). Rates of UGIT endoscopy (n = 49) in patients receiving 10 mg were 0.6% (brand), 1.1% (generic A), and 1.6% (generic B), with generic B higher (IRR 2.88; 95% CI 1.14 to 7.29) in the entire cohort, but not among new users (n = 273) of gastric drugs (IRR 2.46; 95% CI 0.55 to 11.05). Endoscopic findings were normal in 22 patients, hiatal hernia with no mucosal lesion was present in 10 patients, and there was mild-to-moderate esophagitis or gastritis in 17 patients; there were no significant differences among the formulations.

CONCLUSIONS:
We found insufficient evidence to indicate major differences in UGIT adverse effects related to use of daily generic, as compared with brand, alendronates.
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Patient safety

In Vitro Fertilization and Risk of Breast and Gynecologic Cancers: A Retrospective Cohort Study within the Maccabi Healthcare Services

Brinton L, Trabert B, Lunnenfeld E, Sella T, Shalev V, Chodick G.
Fertility and Sterility 2013;99:1189-96.
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.
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Ocular adverse effects of systemic treatment with isotretinoin.

Neudorfer M, Goldshtein I, Shamai-Lubovitz O, Dadon Y, Chodick G, Shalev V.
Archives of Dermatology 2012 in press
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In vitro release of interferon-gamma from peripheral blood lymphocytes in cutaneous adverse drug reactions.

Goldberg I, Hanson M, Chodick G, Shirazi I, Brenner S.
Clinical and Developmental Immunology 2012;2012:687532
ABSTRACT
Cutaneous drug reactions are common but diagnostically challenging due to phenotypic heterogeneity and simultaneous exposure to multiple drugs. These limitations prompted the development of diagnostic tests. Aims. To evaluate the performance of an in vitro assaymeasuring interferon-gamma release frompatients’ lymphocytes in the presence of causative drugs for the diagnosis of drug reactions. Methods. Mononuclear cells derived from patients were incubated with and without suspected drugs, and increment of interferon-gamma levels was measured by ELISA. We performed a telephonic survey to evaluate the effect of stopping the drugs incriminated by the assay on cutaneous manifestations. Results. We assessed 272 patients who used 1035 medications.When assessed against the questionnaire data collected at least 6 months after stopping the causative drug, sensitivity was found to be 83.61% and specificity 92.67%. Likelihood ratio for a positive test is 11.40 and for a negative test 0.18. Positive predictive value is 75.37% and negative predictive value is 95.47%. The test was found to performsignificantly better in males and in older patients. Conclusions. Interferon-gamma release test is a useful adjunct tool in the diagnosis of utaneous drug reactions.
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Adherence to treatment with Selective Serotonin Reuptake Inhibitors and the risk for fractures and bone loss: a population based cohort study

Zucker I, Chodick G, Grunhausd L, Raz R, Shalev V.
CNS Drugs 2012;26:537-547
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The percentage of nosocomial-related out of total hospitalizations for rotavirus gastroenteritis and its association with hand hygiene compliance.

Waisbourd-Zinman O, Ben-Ziony S, Solter E, Chodick G, Ashkenazi S, Livni G.
American Journal of Infection Control 2011;39:166-8
ABSTRACT
Because the absolute numbers of both community-acquired and nosocomial rotavirus gastroenteritis (RVGE) vary, we studied the percentage of hospitalizations for RVGE that were transmitted nosocomially as an indicator of in-hospital acquisition of the infection. In a 4-year prospective study, the percentage of nosocomial RVGE declined steadily, from 20.3% in 2003 to 12.7% in 2006 (P = .001). Concomitantly, the rate of compliance with hand hygiene increased from 33.7% to 49% (P = .012), with a significant (P < .0001) inverse association noted between the two trends.

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Micro-inflammatory changes in asymptomatic healthy adults during bouts of

Steinvil A, Berliner S, Bromberg M, Cohen M, Shalev V, Shapira I, Rogowski O.
Atherosclerosis. 2009 Sep;206(1):270-5.
ABSTRACT
OBJECTIVE:
To explore the possibility that mild inflammatory changes exist in asymptomatic adults during bouts of acute respiratory tract infections in the general population, and may mediate atherothrombotic events.

METHODS:
An epidemiological study that enrolled 5315 males and 2795 females attending a routine screening health program between the years 2003 and 2007. We correlated the concentrations of high sensitivity C-reactive protein (hs-CRP) and quantitative fibrinogen in completely asymptomatic and non-inflamed adults to the weekly epidemiological data for the incidence of acute respiratory tract infections in the community.

RESULTS:
Significant seasonal variations in the inflammatory variables were found for both genders. The population's weekly rates of acute respiratory tract infection had a significant epidemiological influence on the inflammatory biomarkers in the asymptomatic cohort. The magnitude of this influence could reach as much as 12% (3-22%) in hs-CRP concentrations in women and 0.30 micromol/L (0.20-0.41) in fibrinogen concentrations in men, for the change between the mean August and the mean January population's respiratory illness burden.

CONCLUSION:
Increase in the concentrations of two inflammation-sensitive biomarkers can occur in completely asymptomatic adults at times of increased burden of acute respiratory tract infection in the general population. The possibility exists that these inflammatory changes represent occult and asymptomatic infections that could by themselves trigger acute atherothrombotic events.
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Hepatotoxicity rates do not differ in patients with rheumatoid arthritis and psoriasis treated with methotrexate

Amital H, Arnson Y, Chodick G, Shalev V.
Rheumatology (Oxford). 2009;48:1107-10
ABSTRACT
OBJECTIVE:
MTX hepatotoxicity is considered to occur more frequently in patients with psoriasis than in patients with RA. However, toxicity guidelines are based on reports from studies with small sample sizes and limited follow-up periods. The current study's objective was to examine the long-term risk of MTX hepatotoxicity based on a database review of patients with RA or psoriasis, and to examine whether the two populations differed.

METHODS:
We conducted a retrospective cohort review among members of a large health maintenance organization (HMO) in Israel who were diagnosed with either RA (n = 119) or psoriasis (n = 690) and who had purchased at least one dose of MTX. Liver function analyses were performed serially in these patients during the follow-up. All abnormal assays were recorded in the computerized database of the HMO.

RESULTS:
Both groups had hepatic enzyme elevation; the pre-disposing factors predictive of liver damage were female gender and a higher cumulative dose of MTX (hazard ratios, 1.46 and 1.07, respectively, P < 0.001). Age, concurrent diseases and type of disease had no influence on susceptibility to liver damage. No statistically significant difference was detected in any abnormal liver function test among patients with either RA or psoriasis.

CONCLUSION:
Our study did not corroborate previous findings of significant differences between psoriasis patients and RA patients concerning susceptibility to hepatotoxicity from MTX therapy. The only significant factor predicting a higher risk of hepatic damage was female gender.
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Pemphigus variant associated with penicillin use: a case-cohort study of 363 patients from Israel.

Heymann AD, Chodick G, Kramer E, Green M, Shalev V.
Archives Dermatology 2007 ;143:704-7
ABSTRACT
OBJECTIVE:
To determine whether medication use is associated with the development of a pemphigus variant.

DESIGN:
Population-based case-cohort study.

SETTING:
Health maintenance organization in Israel.

METHODS:
All incident pemphigus variant cases diagnosed from January 1, 1997, through December 31, 2001, among 1.5 million members were identified. A cohort of 150,000 was randomly selected from the health maintenance organization population as the control group. Data on case patients and control subjects, including all medication purchased during the 6 months before the diagnosis, were obtained using the health maintenance organization's central database.

RESULTS:
We identified a total of 363 case patients diagnosed as having pemphigus during the 5-year study (6,961,853 person-years of follow-up). The mean age at diagnosis was 49.8 (SD, 22.7) years, and 53% of the cases were women. Results of a multivariate analysis showed that increased risk for pemphigus was associated with purchasing penicillin during the 6 months before the diagnosis (odds ratio, 2.03; 95% confidence interval, 1.56-2.64). Compared with individuals with no penicillin purchases, we calculated increased risks of 1.84 (95% CI, 1.36-2.49) and 3.02 (95% CI, 1.41-6.49) in those with 1 and 3 or more purchases, respectively. None of the other examined medications, including cephalosporins, angiotensin-converting enzyme inhibitors, dipyrone, anticonvulsants, and nonsteroidal anti-inflammatory drugs, showed similar risks.

CONCLUSIONS:
To our knowledge, the present research is one of the largest published epidemiological studies on pemphigus variant. The use of computerized medical and administrative databases allowed the detection of case patients in the community, resulting in a higher calculated incidence rate than previously reported. The findings suggest a relationship between the use of penicillin and pemphigus variant. Further studies to assess the nature of this statistical association are warranted.
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Excess Lifetime Cancer Mortality Risk Attributable to Radiation Exposure from Pediatric CT Examinations.

Chodick G, Ronckers C, Ron E, Shalev V.
Israel Medicine Association Journal 2007;9:584-7
ABSTRACT
BACKGROUND:
The use of computed tomography in Israel has been growing rapidly during recent decades. The major drawback of this important technology is the exposure to ionizing radiation, especially among children who have increased organ radiosensitivity and a long lifetime to potentially develop radiation-related cancer.

OBJECTIVE:
To estimate the number of excess lifetime cancer deaths related to annual CT scans performed in children in Israel.

METHODS:
We used CT scan utilization data from 1999 to 2003 obtained from the second largest health management organization in the country to project age and gender-specific CT scan use nationwide. Based on published organ doses for common CT examinations and radiation-related cancer mortality risk estimates from studies in survivors of the atomic bomb, we estimated the excess lifetime risks for cancer mortality attributed to use of CT in children and adolescents (up to 18 years old) in Israel.

RESULTS:
We estimated that 17,686 pediatric scans were conducted annually in Israel during 1999-2003. We project that 9.5 lifetime deaths would be associated with 1 year of pediatric CT scanning. This number represents an excess of 0.29% over the total number of patients who are eventually estimated to die from cancer in their lifetime.

CONCLUSIONS:
Pediatric CT scans in Israel may result in a small but not negligible increased lifetime risk for cancer mortality. Because of the uncertainty regarding radiation effects at low doses, our estimates of CT-related cancer mortality should be considered with caution. Nevertheless, physicians, CT technologists, and health authorities should work together to minimize the radiation dose for children to as low as reasonably achievable and encourage responsible use of this essential diagnostic tool.
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Comparative Effectiveness and Outcomes Research

Rotavirus immunization and type 1 diabetes mellitus: A nested caseecontrol study

Chodick G, Almog M, Ashkenazi S, Sella T.
Pediatric Infectious Disease 6 (2014)147-149.
ABSTRACT
The objective of the present nested caseecontrol study was to assess whether rotavirus vaccination is associated with reduced risk of Type 1 diabetes mellitus (T1DM). Using clinical database of a large health organization in srael, we identified all incident cases of T1DM that were born during the period spanning January 2008 to June 2010, and diagnosed before March 2012. For each case, we selected up to three control individuals without T1M that were individually matched on the exact date of birth. A total of 16 eligible T1DM cases were detected and 5 matched controls. After adjusting to residence area in Israel, the odds ratio for T1DM associated with full vaccination against rotavirus was 7.38 (95%: 1.19e45.62, P ¼ 0.032). The results of the present study do not upport the conclusion that childhood immunization with rotavirus vaccine is associated with reduced risk of T1DM.
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The association between the serum levels of uric acid and alanine aminotransferase in a population-based cohort.

Zelber-Sagi S, Ben-Assuli O, Rabinowich L, Goldstein A, Magid A, Shalev V, Shibolet O, Chodick G.
Liver International (2015).
ABSTRACT
Background & Aims: Elevated serum uric acid levels reflect and also cause both oxidative stress and insulin resistance and are frequently observed in patients with the metabolic syndrome. A strong association exists between the metabolic syndrome and non-alcoholic fatty liver disease (NAFLD). Therefore, we aimed to test the association between uric acid and elevated alanine aminotransferase (ALT), as a surrogate for NAFLD, using real-world data.
Methods: Data used for the cross-sectional study were obtained from Maccabi Healthcare System, a 2-million member health maintenance organization in Israel. The population consisted of individuals aged 20–60 years who underwent blood tests for ALT and uric acid between 1997 and 2012. Individuals with secondary liver disease, celiac, and inflammatory bowel-disease were excluded. Subgroup analysis was performed in subjects who were given the diagnosis of fatty liver in their medical records (n = 2628).
Results: The study population included 82 608 people (32.5% men, mean age 43.91 ± 10.15 years). There was a significant positive doseresponse association between serum uric acid levels and the rate of elevated serum ALT (P for trend <0.001). In multivariable model, controlling for potential confounders, the association between uric acid and elevated ALT persisted (OR = 2.10, 95% CI 1.93–2.29, for the fourth quartile vs. the first). This association was maintained in all categories of gender and BMI. Similar results were observed among patients diagnosed with fatty liver (OR = 1.77, 1.22–2.57).
Conclusions: Serum uric acid is independently associated with elevated ALT, as a surrogate for NAFLD, and thus may serve as a serum marker for liver damage and should be further investigated as a risk factor for NAFLD.
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The change in the incidence of outpatient visits due to all cause and rotavirus gastroenteritis in children aged less than five years following the introduction of universal vaccination program in Isr

Muhsen K, Chodick G, Goren S, Anis E, Ziv T, Shalev V, Cohen D.
Eurosurvelliance 2015.
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Continuation with statins therapy and the risk of primary cancer: A population-based study.

Lutski M, Shalev V, Chodick G.
Preventative Chronic Diseases 2012 in press
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Adherence to Statins is associated with reduced incidence of idiopathic venous thromboembolism: real-life data from a large healthcare maintenance organization

Rabinowich L, Steinvil A, Leshem-Rubino E, Berliner S, Zeltser D, Rogowski O, Shalev V, Raz R, Chodick G.
Heart 2012;98:1817-21
ABSTRACT
Objective Previous reports on the association between statin use and venous thromboembolism (VTE) did not examine patient adherence to medications, thus their applicability in a real life setting is questionable. Our objective was to investigate the association between the use of statins and incidence of first ever idiopathic VTE.

Design A retrospective cohort study.

Settings A large healthcare maintenance organisation.

Patients Included were statin initiators aged 30 years or older since 2003 who did not have a statin prescription for at least 4 years before that and had at least 18 months follow-up. Excluded were patients with known risk factors for VTE. End of follow-up was defined as the first of the following: leaving Maccabi Healthcare Services, death, VTE or October 27, 2010.

Interventions Prescription drug purchase data was analysed in order to evaluate the association between statin use and adherence and between VTE prevention.

Main outcome measures VTE diagnosis during follow-up.

Results The study population included 127 822 subjects (53 618 females). The follow-up period was comprised of 594 190 patient years, and included 1375 VTE cases and 5-year cumulative incidence rate of 1.15%. Cox regression analysis demonstrated a significantly lower VTE risk of 19% and 22% in the more adherent patient groups, compared to the risk for the lowest adherence group. The simvastatin dose, the most frequently prescribed statin, was negatively associated with the risk of VTE.

Conclusions In a real life healthcare maintenance organisation setting, better adherence to statins is associated with a reduced risk of first ever idiopathic VTE events.
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Persistence with statins and onset of rheumatoid arthritis: A population-based cohort study.

Chodick G, Amital H, Shalem Y, Kokia E, Heymann AD, Porath A, Shalev V.
PLoS Med. 2010 Sep 7;7(9):e1000336.
ABSTRACT
BACKGROUND:
The beneficial effects of statins in rheumatoid arthritis (RA) have been suggested previously, but it is unclear whether statins may prevent its development. The aim of this retrospective cohort study was to explore whether persistent use of statins is associated with onset of RA.

METHODS AND FINDINGS:
The computerized medical databases of a large health organization in Israel were used to identify diagnosed RA cases among adults who began statin therapy between 1998 and 2007. Persistence with statins was assessed by calculating the mean proportion of follow-up days covered (PDC) with statins for every study participant. To assess the possible effects of healthy user bias, we also examined the risk of osteoarthritis (OA), a common degenerative joint disease that is unlikely to be affected by use of statins. A total of 211,627 and 193,770 individuals were eligible for the RA and OA cohort analyses, respectively. During the study follow-up period, there were 2,578 incident RA cases (3.07 per 1,000 person-years) and 17,878 incident OA cases (24.34 per 1,000 person-years). The crude incidence density rate of RA among nonpersistent patients (PDC level of <20%) was 51% higher (3.89 per 1,000 person-years) compared to highly persistent patients who were covered with statins for at least 80% of the follow-up period. After adjustment for potential confounders, highly persistent patients had a hazard ratio of 0.58 (95% confidence interval 0.52-0.65) for RA compared with nonpersistent patients. Larger differences were observed in younger patients and in patients initiating treatment with high efficacy statins. In the OA cohort analysis, high persistence with statins was associated only with a modest decrement in risk ratio (hazard ratio = 0.85; 0.81-0.88) compared to nonadherent patients.

CONCLUSIONS:
The present study demonstrates an association between persistence with statin therapy and reduced risk of developing RA. The relationship between continuation of statin use and OA onset was weak and limited to patients with short-term follow-up.
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Persistence with statins and incident cataract: A population-based historical cohort study

Chodick G, Heymann AD, Flash S, Kokia E, Shalev  V.
Annals of Epidemiology 2010; 20: 136-­142
ABSTRACT
PURPOSE:
In recent years, there is a growing body of evidence suggesting that statins may have anti-inflammatory effects; consequently, it was hypothesized that statins may have a preventive effect against cataract.
METHODS:
The study was carried out on a retrospective cohort of 180,291 new statin users in a large health organization in Israel. Study participants were followed between 1998 and 2007 for incident cataract or cataract extraction.
RESULTS:
During the study period 27,301 cataracts were diagnosed and 6,976 cataract extractions were performed among study participants. Persistence with statins was associated significantly (P < 0.001) with a reduced risk of cataract in men and women aged 45 to 74. Men aged 45-54 with a high (>80%) proportion of follow-up days covered with statins had an adjusted hazard ratio of 0.62 (95% confidence interval: 0.54-0.72), compared with patients with low persistence with statins. In elderly patients, no relationship or a positive relationship was observed.
CONCLUSIONS:
Persistent statin use was significantly protective for the incidence of cataract in men and women under 75 years of age.
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Persistence with statins and all-­cause mortality: A population-­based cohort study

Shalev V, Chodick G (equal contribution), Silber H, Kokia E, Jan J, Heymann AD.
Archives of Internal Medicine 2009;169:260-8.
ABSTRACT
BACKGROUND:
The beneficial effects of statins on cardiovascular mortality in secondary prevention have been established in several long-term, placebo-controlled trials. However, the value of statin therapy in reduction of overall mortality in patients without coronary heart disease (CHD) is questionable. This study evaluated the effect of statin therapy in subjects with no indication of cardiovascular disease (primary prevention) and patients with known CHD (secondary prevention).

METHODS:
This retrospective cohort study included 229 918 adult enrollees in a health maintenance organization in Israel who initiated statin treatment from 1998 through 2006 (mean age, 57.6 years; 50.8% female). Proportion of days covered (PDC) with statins was measured by the number of dispensed statin prescriptions during the interval between the date of the first statin prescription and the end of follow-up.

Results:
During the study period 27,301 cataracts were diagnosed and 6,976 cataract extractions were performed among study participants. Persistence with statins was associated significantly (P < 0.001) with a reduced risk of cataract in men and women aged 45 to 74. Men aged 45-54 with a high (>80%) proportion of follow-up days covered with statins had an adjusted hazard ratio of 0.62 (95% confidence interval: 0.54-0.72), compared with patients with low persistence with statins. In elderly patients, no relationship or a positive relationship was observed.

RESULTS:
During a mean of 4.0 and 5.0 years of follow-up, there were 4259 and 8906 deaths among the primary prevention and secondary prevention cohorts, respectively. In both cohorts, continuity of treatment with statins (PDC, > or =90%) conferred at least a 45% reduction in risk of death compared with patients with a PDC of less than 10%. A stronger risk reduction was calculated among patients with high baseline low-density lipoprotein cholesterol level and patients initially treated with high-efficacy statins.

CONCLUSIONS:
Better continuity of statin treatment provided an ongoing reduction in mortality among patients with and without a known history of CHD. The observed benefits from statins were greater than expected from randomized clinical trials.
KEYWORDS
aspirin • colorectal cancer • odds ratio • polyps
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Late influenza vaccination is associated with reduced effectiveness

Chodick G, Heymann AD, Green MS, Kokia E, Shalev V
Preventive Medicine 2006;43:71-­6
ABSTRACT
BACKGROUND:
Extensive research has been carried out to quantify the efficacy and immunologic responses to influenza immunization, however, only little was reported on whether the timing of vaccine administration affects its effectiveness. The study aims were to compare post-immunization hospitalization and mortality rates among high-risk patients who were vaccinated against influenza in different periods of autumn.

METHODS:
Data for the current population-based historical prospective study were obtained from a large health organization in Israel insuring 1,600,000 members. Study population (n = 68,166) included high-risk patients aged 55 and above, who were immunized against influenza between October and November 2003.

RESULTS:
Although at baseline, individuals vaccinated in late November (12-25/11/2003) were significantly younger and had lower burden of illness compared to those vaccinated in early October (1-13/10/2003), they had higher hospitalization rates and longer hospital stay during the following winter (December to March). They also had an increased risk for all-cause mortality (RR = 1.78; 95%CI: 1.13-2.80). No such differences were observed during the following summer (April-August).

CONCLUSIONS:
In countries where influenza generally peaks between December and early March, vaccines administered after mid-November might be less beneficial.
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The use of organizational data for the evaluation of mass prevention programs

Heymann AD, Tarashansky I, Kokia E, Chodick G
Preventive Medicine 2004;39: 1143-­1147
ABSTRACT
BACKGROUND:
The effectiveness of health promotion campaigns is hard to measure due to complex outcome and external factors. This study presents a method to evaluate a mass women's health promotion campaign held in a large health maintenance organization (HMO) in Israel.

METHODS:
This population-based study used administrative and medical databases to examine whether postal invitation to 120,231 HMO-female members increased adherence with certain preventive medicine recommendations (LDL-C, bone density test, and mammography breast cancer screening). A comparison was made using three different reference data: pre- and post-campaign periods (1998-2003), HMO-male members who were not targeted by the campaign, and rates of urine tests, which were also not targeted by the campaign.

RESULTS:
During the 2 months following the campaign, adherence with mammography (3.8%) and LDL-C (12.5%) reached their maximum rates in 5 years. Adherence with bone density test increased from 2.3% in 2000 to 2.8% in the campaign period. No similar trends were observed for urine or LDL-C tests among men.

CONCLUSIONS:
The use of multiple reference groups through the analysis of administrative and medical databases supports the association between the campaign and improved adherence with screening tests. A similar methodology may be adopted for the analysis of mass health promotion campaigns in large HMOs.
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Influenza vaccination: reduction in hospitalizations and death rates among members of "Maccabi Healthcare Services" during the 2000-2001 influenza season.

Shapiro J, Shemer S, Hyman A, Shalev V, Maharshak N, Chodik G, Green M, Kokia E  
Israel Medicine Association Journal 2003;5:706-­708
ABSTRACT
BACKGROUND:
Upper respiratory tract illnesses have been associated with an increased risk of morbidity and mortality.

OBJECTIVE:
To assess the influence of vaccination against influenza on the risk of hospitalization in internal medicine and geriatric wards, and the risk of death from all causes during the 2000-2001 influenza season.

METHODS:
A historical cohort study was conducted using computerized general practitioner records on patients aged 65 years and above, members of "Maccabi Healthcare Services"--the second largest health maintenance organization in Israel with 1.6 million members. The patients were divided into high and low risk groups corresponding to coexisting conditions, and were studied. Administrative and clinical data were used to evaluate outcomes.

RESULTS:
Of the 84,613 subjects in the cohort 42.8% were immunized. At baseline, vaccinated subjects were sicker and had higher rates of coexisting conditions than unvaccinated subjects. Vaccination against influenza was associated with a 30% reduction in hospitalization rates and 70% in mortality rates in the high risk group. The NNT (number needed to treat) measured to prevent one hospitalization was 53.2 (28.2 in the high risk group and 100.4 in the low risk group). When referring to length of hospitalization, one vaccine was needed to prevent 1 day of hospitalization among the high risk group. Analyses according to age and the presence or absence of major medical conditions at baseline revealed similar findings across all subgroups.

CONCLUSIONS:
In the elderly, vaccination against influenza is associated with a reduction in both the total risk of hospitalization and in the risk of death from all causes during the influenza season. These findings compel the rationale to increase compliance with recommendations for annual influenza vaccination among the elderly.
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Healthcare services research

The Invisible Patient: Characteristics of Elderly People who do not visit Primary Care Physicians

Eshel N, Raz R, Chodick G, Guindy M.
The Israel Journal of Health Policy Research 2013;2:7
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Determinants of cost-related non-adherence to medications among chronic patients in Maccabi healthcare services, Israel.

Simon-Tuval, Triki N, Chodick G, Greenberg D.
Value in Health In Press
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Performance of Pap smears among women in a large Israeli HMO during the years 2006-2008

Raz R, Shavit O, Stein M, Cohen R, Schejter E, Chodick G, Shalev V.
Public Health 2012;126:594-599
ABSTRACT
Objectives
The Papanicolaou (Pap) smear test is used in many countries as a screening procedure for cervical cancer and precancerous lesions. The actual uptake of this screening test among women at risk for cervical cancer is unknown. The aim of this study was to estimate the percentage of women who are screened by Pap smears from the relevant population at risk, and to detect factors that are independently associated with uptake of cervical screening.

Study design
Retrospective database study.

Methods
This study was undertaken at Maccabi Healthcare Services (MHS), the second largest publicly funded health maintenance organization in Israel. The study population consisted of Israeli women aged 21–59 years who were insured by MHS between 2006 and 2008. Logistic regression analyses were used to determine the independent relationships between immigration and socio-economic status and cervical screening.

Results
The study population included 489,663 women who had a total of 313,602 Pap smears between 2006 and 2008. Fifty-four percent of the women did not have a Pap smear during the study period, 32% had at least one smear, and 14% had at least two smears. Living in a low socio-economic neighbourhood and recent immigration were independently and negatively associated with screening uptake.

Conclusion
Despite the clinical guidelines and the low costs, many Israeli women who are at risk for cervical cancer are not screened.
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Smoking and Other Correlates of Health Care Services Utilization Among Mandatory Military Recruits in Israel.

Levine H, Huerta-Hartal M, Bar-Ze'ev Y, Balicer RD, Auster O, Ankol OE, Chodick G
Nicotine Tob Res. 2012 Mar 1.
ABSTRACT
INTRODUCTION: Data on utilization of ambulatory care and the impact of lifestyle on health among young adults are scarce. Israeli mandatory military service provides a unique opportunity to investigate these topics. Study objective was to analyze the utilization of health care services (HCS) during the first year of military service, and its associations with health behavior at recruitment, in order to plan health services, health classification, and health promotion activities.

METHODS: We conducted a retrospective cohort study among a representative sample of 5,751 mandatory new recruits between January 1, 2004, and December 31, 2008. Data were collected from the Israeli Defense Force computerized medical and administrative records and from an ongoing health survey among military recruits.

RESULTS: During their first year of service, recruits had, on average, more than 7 visits to the primary care clinic, more than 10 dispensed nonchronic medications, and more than 5 days of sick leave. Female sex (OR = 1.27; 1.06-1.51) and current cigarette smoking (OR = 1.57; 1.34-1.84) were significantly associated with increased use of HCS, after controlling for possible confounders.Conclusions:Our findings indicate high utilization of HCS during the first year of military service and highlight the potential effect of cigarette smoking as a risk factor for increased morbidity among apparently healthy young adults. These findings support adding smoking status to fitness assessments and could aid health promotion efforts to reduce smoking rates among adolescents.

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The utilization of pediatric computed tomography in a large Israeli HMO.

Chodick G, Ronckers C, Ron E, Shalev V
Pediatric Radiology 2006; 36:485-490
ABSTRACT
BACKGROUND:
Concern has been raised about the potential risks related to radiation exposure from CT scans, particularly among children. However, to date, there are few data available describing the magnitude of pediatric CT utilization.

OBJECTIVE:
The aim of the study was to explore patterns of CT use in pediatric patients, with respect to time, use of multiple scans, body regions imaged, and medical diagnoses.

MATERIALS AND METHODS:
Records of 22,223 scans performed on 18,075 people aged < or =18 years over the period 1999-2003, including diagnoses recorded within 21 days after the examination, were obtained from a large Israeli Health Maintenance Organization (1,600,000 members).

RESULTS:
The highest annual CT examination rate (per 1,000) was recorded in 2001 (10.1) compared to 7.0 and 6.3 in 1999 and 2003, respectively. The lowest rate (three scans per 1,000) was found for 3-year-old children, with increasing rates with age. The head was the most frequently scanned region, both in young children (78%) and adolescents (39%). Symptoms of ill-defined conditions and injuries were documented in 22% and 10% of all scans, respectively.

CONCLUSIONS:
Although the results suggest that children comprise only 3% of all patients undergoing CT, this important modality must be carefully used because of their increased radiosensitivity
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Gender differences in healthcare utilization and medical indicators among patients with diabetes.

Shalev V, Chodick G, Heymann AD, Kokia E.
Public Health 2005; 119:45-49.
ABSTRACT
OBJECTIVE:
To describe differences in healthcare utilization and health indicators of patients with diabetes, according to gender.

STUDY DESIGN:
A population-based outcome study conducted on 21,277 diabetic patients between the ages of 45 and 64 years who are members of the second largest health maintenance organization in Israel.

METHODS:
Data on healthcare utilization (process indicators) and health problems (outcome indicators) were obtained from computerized medical records that are stored routinely by the organization. The study period was the year 2002.

RESULTS:
Significantly (P < 0.05) lower healthcare utilization was observed in men compared with women for all indicators examined (number of visits to physicians and the performance of urine, lipids and creatinine tests). Nonetheless, men showed better health outcomes (lower low-density lipoprotein cholesterol, triglycerides, HbA1c).

CONCLUSIONS:
Women who suffer from diabetes use more healthcare services and have a higher morbidity rate compared with men. Future research should seek to identify the factors contributing to this observation, which can potentially make an important contribution to the development of disease management strategies that target diabetic women.
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Influence of school closure on the incidence of viral respiratory diseases among children and on health care utilization.

Heymann A, Chodick G, Reichman B, Kokia E, Kramer E, Shermer J.
Pediatric Infectious Disease Journal 2004;23: 675-677
ABSTRACT
We evaluated the effect of school closure on the occurrence of respiratory infection among children ages 6-12 years and its impact on health care services. During this period, there were significant decreases in the diagnoses of respiratory infections (42%), visits to physician (28%) and emergency departments (28%) and medication purchases (35%). The present study provides quantitative data to support school closure during an influenza pandemic.
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Medical informatics and computer-­assisted management

The impact of residents' training in Electronic Medical Record (EMR) use on their competence: report of a pragmatic trial.

Reis S, Sagi D, Eisenberg O, Kuchnir Y, Azuri J, Shalev V, Ziv A.
Patient Educ Couns. 2013;93:515-21
ABSTRACT
Objectives
Even though Electronic Medical Records (EMRs) are increasingly used in healthcare organizations there is surprisingly little theoretical work or educational programs in this field. This study is aimed at comparing two training programs for doctor–patient–computer communication (DPCC).

Methods
36 Family Medicine Residents (FMRs) participated in this study. All FMRs went through twelve identical simulated encounters, six pre and six post training. The experiment group received simulation based training (SBT) while the control group received traditional lecture based training.

Results
Performance, attitude and sense of competence of all FMRs improved, but no difference was found between the experiment and control groups. FMRs from the experiment group evaluated the contribution of the training phase higher than control group, and showed higher satisfaction.

Conclusion
We assume that the mere exposure to simulation served as a learning experience and enabled deliberate practice that was more powerful than training. Because DPCC is a new field, all participants in such studies, including instructors and raters, should receive basic training of DPCC skills.

Practice implication
Simulation enhances DPCC skills. Future studies of this kind should control the exposure to simulation prior to the training phase. Training and assessment of clinical communication should include EMR related skills.
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The use of an automated patient registry to manage and monitor cardiovascular conditions and related outcomes in a large health organization.

Shalev V, Chodick G, Goren I, Silber H, Kokia E, Heymann AD.
Int J Cardiol. 2011 Nov 3;152(3):345-9.
ABSTRACT
BACKGROUND: The present study describes a computerized registry of cardiovascular disease patients in a large health maintenance organization in Israel. The registry is aimed to be used by health professionals to identify cardiovascular disease patients and to follow the courses of their illnesses and risk factors.

METHODS: In 1998, the registry was initiated using advanced information technology that integrated personal computerized community and hospital records, data from laboratory tests, dispensed medications, physiological signals, radiological images, and reports from investigations and procedures.

RESULTS: Between 1998 and 2007, the number of patients with cardiovascular diseases that were identified by the registry has increased from 34,144 to 80,339. During this period, the age-adjusted prevalence rates have risen from 3.7% to 5.1% and from 1.9% to 2.6%, among men and women, respectively. The percentage of ischemic heart disease patients who reached target LDL was doubled, from 21% in 2000 to 50% in 2006. The average stay in hospital declined from 11.7 to 8.6 days. Primary myocardial infarction rates declined 33% and 54% in men aged 54-65 and women aged 65-74 years, respectively.

CONCLUSIONS: The present study provides, for the first time in Israel, data on selected quality of care and clinical outcomes using a large, population-based registry of cardiovascular disease patients. It demonstrates a significant improvement in the adherence with LDL tests and achieving target LDL levels and a subsequent decline in incidence of myocardial infarction within ten years since its establishment.

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Format change of a laboratory test order form affects physician behavior

Shalev V, Chodick G, Heymann AD.
International Journal of Medical Informatics 2009;78:639-44
ABSTRACT
PURPOSE:
Our study was designed to find whether a change in physician ordering of laboratory testing could be obtained by the simple strategy of changing the set-up of the check-box laboratory order form that is embedded in a computerized medical record.

METHODS:
This prospective intervention study was undertaken in Maccabi Healthcare Services, a Preferred Provider Organization that has used a computerized medical record since 1992. We examined data from 865 primary healthcare physicians over 3 years. In May 2005 we changed the order form and reduced the number of tests that can be ordered using a check-box form from 51 to 26. Twenty-seven tests were removed from the form and two tests were added. The total number of laboratory test orders and the median rate of test orders per visit to physician during each of the study periods were calculated separately for each test.

RESULTS:
Tests that were added to the computerized laboratory order form showed an increase of 60.7% in the first year and a further 90% increase in the following year. For the unchanged tests the percentage changes over the same periods were +18.4% and -22.4%. For the deleted tests the change was -27% and -19.2% for the respective years.

CONCLUSIONS:
Changes in format of laboratory test order forms can change physician test ordering and may be useful together with other interventions to improve appropriateness of laboratory testing. A thoughtfully built test ordering form can reinforce clinical guidelines for the performance of some preventive testing and follow-up.
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The implementation of managed care for diabetes using medical informatics in a large Preferred Provider Organization.

Heymann AD, Chodick G, Halkin H, Karasik A, Shalev V, Shemer J, Kokia E.
Diabetes Research Clinical Practice 2006;71:290-8
ABSTRACT
BACKGROUND:
It has been demonstrated by meta analysis that if a regular review of patients is guaranteed, the standard of primary care can be as good or better than hospital outpatient care, however, empirical data suggests that compliance with diabetes clinical practice recommendations is inadequate in primary care. This study describes the reorganization of diabetes care using disease management principles in a Preferred Provider Organization (PPO) operating on a country-wide basis in which each diabetes clinic became responsible for the overall care of all patients with diabetes.

METHODS:
This descriptive pre and post change study was undertaken in a large public-funded PPO insuring over one and half million individuals. The study was possible due the use of a centralized electronic disease registry which enabled the collection of all patient data. Several markers, such as HbA1C and LDC-cholesterol levels, were used to assess the quality of care for the diabetic patients.

RESULTS:
Mean HbA1C results of the cohort showed a continuous reduction from 8.1% (S.D. = 1.55) in 1999 to 7.68% (S.D. = 1.47) in 2002 and to 7.79 (S.D. = 1.54) in 2004. Improved results were also recorded for LDL-C 126.37 (S.D. = 35.16) in 1999 to 114.74 (S.D. = 34.49) in 2002, and to 113.39 (S.D. = 33.8) in 2004. The number of diabetic patients seen by the diabetologist increased by 62% over this period, despite an increase in diabetologist work hours of only 23%.

CONCLUSION:
The reorganization of health delivery for diabetic patients within a country-wide PPO, based on the principles of disease management and supported by medical informatics improves quality of care.
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Countrywide computer alerts to community physicians improve potassium testing in patients receiving diuretics.

Hoch I, Heymann AD, Kurman I, Valinsky LJ, Chodick G, Shalev V.
Journal of American Medical Informatics Association 2003;10:541-546
ABSTRACT
More than 20% of approximately 35,000 patients filling a diuretic prescription had no potassium blood test recorded within the previous year. A laboratory reporting system used throughout Israel by Maccabi Healthcare Services physicians was modified to provide physician alerts regarding potassium testing. The physicians were experienced users of a computerized medical record (CMR) that provided online laboratory test results. A nightly batch file checked pharmacy diuretic purchases against the patient's potassium blood test status. On-screen computer-generated reminders were sent to physicians of patients lacking a recent potassium test. Reminders to clinicians increased potassium testing by 9.8% (p < 0.001). Physician age and gender played a small part in predicting compliance to the alert, but specialty and practice size did not. The time delay between the date a reminder was sent and the potassium test date decreased steadily during the intervention. The success of this reminder system encourages expansion to include more drug-laboratory interactions. Furthermore, direct alerts to patients at multiple organization/patient contact points are planned.
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Post-­marketing Surveillance

Perceptions of hypertension treatment among patients with and without diabetes.

Heymann A, Valinsky L, Inbar Z, Gabriel C, Varda S.
BMC Fam Pract. 2012 Mar 26;13(1):24.
ABSTRACT
BACKGROUND: Despite the availability of a wide selection of effective antihypertensive treatments and the existence of clear treatment guidelines, many patients with hypertension do not have controlled blood pressure. We conducted a qualitative study to explore beliefs and perceptions regarding hypertension and gain an understanding of barriers to treatment among patients with and without diabetes.

METHODS: Ten focus groups were held for patients with hypertension in three age ranges, with and without diabetes. The topic guides for the groups were: What will determine your future health status? What do you understand by "raised blood pressure"? How should one go about treating raised blood pressure?

RESULTS: People with hypertension tend to see hypertension not as a disease but as a risk factor for myocardial infarction or stroke. They do not view it as a continuous, degenerative process of damage to the vascular system, but rather as a binary risk process, within which you can either be a winner (not become ill) or a loser. This makes non-adherence to treatment a gamble with a potential positive outcome. Patients with diabetes are more likely to accept hypertension as a chronic illness with minor impact on their routine, and less important than their diabetes. Most participants overestimated the effect of stress as a causative factor believing that a reduction in levels of stress is the most important treatment modality. Many believe they "know their bodies" and are able to control their blood pressure. Patients without diabetes were most likely to adopt a treatment which is a compromise between their physician's suggestions and their own understanding of hypertension.

CONCLUSION: Patient denial and non-adherence to hypertension treatment is a prevalent phenomenon reflecting a conscious choice made by the patient, based on his knowledge and perceptions regarding the medical condition and its treatment. There is a need to change perception of hypertension from a gamble to a disease process. Changing the message from the existing one of "silent killer" to one that depicts hypertension as a manageable disease process may have the potential to significantly increase adherence rates.

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Deaths following influenza vaccination—background mortality or causal connection?

Kokia, E, Silverman, B, Green, M, Kedema, H, Guindy, M, Shemer, S.
Vaccine 2007;25: 8557–8561
ABSTRACT
In October 2006, four deaths occurred in Israel shortly after influenza immunization, resulting in a temporary halt to the vaccination campaign. After an epidemiologic investigation, the Ministry of Health concluded that these deaths were not related to the vaccine itself and the campaign resumed; however, vaccine uptake was markedly reduced. Estimates of true background mortality in this high-risk population would aid in public education and quell unnecessary concerns regarding vaccine safety. We used data from a large HMO to estimate mortality in influenza vaccine recipients aged 55 and over during four consecutive winters (2003, 2004, 2005 and 2006). Date of immunization was ascertained from patient treatment files, vital status through Israeli National Insurance Institute data. We calculated crude death rates within 7, 14 and 30 days of influenza immunization, and used a Cox Proportional Hazards Model to estimate the risk of death within 14 days of vaccination, adjusting for age and comorbid conditions (age over 75, history of diabetes or cardiovascular disease, status as homebound patient) in 2006. The death rate among influenza vaccine recipients ranged from 0.01 to 0.02% within 7 days and 0.09-0.10% at 30 days. Influenza immunization was associated with a decreased risk of death within 14 days after adjustment for comorbidities (Hazard ratio, 0.33, 95% CI, 0.18-0.61). Our findings support the assumption that influenza vaccination is not associated with increased risk of death in the short term.
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Use of a computerized database to study the effectiveness of an attenuated varicella vaccine

Passwell, J, Hemo, B, Levi, Y, Ramon, R, Friedman, N, Lerner-Geva, L.
Pediatric Infectious Disease Journal, 2004;23:221–6
ABSTRACT
BACKGROUND:
The varicella vaccine Varilrix (GlaxoSmithKline) was introduced in Israel in June 2000 as an optional vaccination for children.

METHODS:
We used the database of a single health maintenance organization that serves 25% of the population in Israel to assess the effectiveness of the vaccine retrospectively. Incidence and complications of varicella were derived from the database from January 1, 1998 until December 31, 2002.

RESULTS:
Since licensure >30000 individuals younger than 10 years in this health maintenance organization have been immunized with the vaccine. Annual incidence of disease per 1000 in the study population was 86.6 in 1998, 74.6 in 1999, 74.0 in 2000, 37.1 in 2001 and 44.6 in 2002. This declining trend in incidence of disease was statistically significant. Complications of varicella occurred in approximately 1% of patients throughout the 5-year study period, but there was a parallel decline in the number of patients with complications corresponding to the decline in disease incidence. Vaccine effectiveness for prevention of clinical disease in this population was 92% (95% confidence interval, 91.0 to 92.7). There were varying rates of utilization within communities of varied socioeconomic class, so that in the higher socioeconomic class there was an increased utilization and a corresponding decrease of attack rate; whereas in communities where there were lower utilization rates, corresponding increased numbers of varicella cases were seen.

CONCLUSION:
This database enables long term follow-up of the effectiveness of this vaccine in a large population.
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