[Show abstract][Hide abstract] ABSTRACT: Objectives To estimate the proportion of patients with renal impairment among postmenopausal osteoporotic women within a large health plan in Israel.
Methods This was a retrospective analysis of Maccabbi electronic medical records (EMR) in Israel. Women aged ≥55 years, with a recorded osteoporosis diagnosis or osteoporosis-related fracture (date for 1st such diagnosis was defined as index date) between 1/1/2007 and 12/31/2012, who were enrolled in health plan for ≥1 year prior to and after index were included. Patients' minimum serum creatinine level (Scr) during one year pre-index to one year post-index was utilized to calculate glomerular filtration rate (eGFR), using Modification of Diet in Renal Disease (MDRD) equation. Stage 1-5 of renal impairment was classified using the MDRD renal impairment staging system by eGFR: normal ≥90; mild 60 – 89; moderate 30– 59; severe 15 – 29, and failure<15 mL/min/1.73 m2 respectively.
Results 18,101 patients were included in the analysis. The mean age (± standard deviation [SD]) of these patients was 66.7±9.0 years, and 35.5% of patients had a fracture at index. Patients with renal function of stage 1-5 accounted for 21.7%, 47.3%, 14.3%, 15.9%, 1.0%, and 0.1% respectively of all patients. 2.3% of those patients had eGFR levels <35 mL/min/1.73 m2; the rate was 1.5% for patients with osteoporosis diagnosis and 3.9% for patients with fractures; the rate was higher among older patients aged ≥70 (4.3%) than younger patients (0.5%).
Conclusions This analysis showed that 2.3% of osteoporotic women had renal impairment (eGFR levels <35 mL/min/1.73 m2) to a level at which the commonly used bisphosphonates such as alendronate, risedronate and ibandronate are not recommended. This limitation indicates a need for therapeutic alternatives that have been demonstrated to reduce fracture risk in osteoporotic patients with severe renal insufficiency.
Disclosure of Interest None declared
Archives of Osteoporosis 12/2015; 10(1):210. DOI:10.1007/s11657-015-0210-y
[Show abstract][Hide abstract] ABSTRACT: Background
The objective was to examine the association of gastrointestinal (GI) events and osteoporosis treatment initiation patterns among postmenopausal women following an osteoporosis diagnosis from an Israeli health plan.Methods
This retrospective analysis of claims records included women aged ≥ 55 years with ≥ 1 osteoporosis diagnosis (date of first diagnosis was index date). Osteoporosis treatment initiation was defined as use of osteoporosis therapy (oral bisphosphonates or other) during 12 months postindex. GI events (diagnosis of GI conditions) were reported for 12 months preindex and postindex (from index to treatment initiation or 1 year postindex, whichever occurred first). The association of postindex GI events (yes/no) with the initiation of osteoporosis treatment (yes/no) and with type of therapy initiated (oral bisphosphonate vs. other) were examined with logistic regression and Cox proportional hazard regression (as sensitivity analysis).ResultsAmong 30,788 eligible patients, 17.5% had preindex GI events and 13.0% had postindex GI events. About 70.6% of patients received no osteoporosis therapy within 1 year of diagnosis, 24.9% received oral bisphosphonates and 4.5% received other medications. Postindex GI events were associated with lower odds of osteoporosis medication initiation (85–86% reduced likelihood; p < 0.01). Upon treatment initiation, postindex GI was not significantly associated with the type of osteoporosis therapy initiated, controlling for baseline GI events and patient characteristics.Conclusions
Among newly diagnosed osteoporotic women from a large Israeli health plan, 70.6% did not receive osteoporosis treatment within 1 year of diagnosis. The presence of GI events was associated with reduced likelihood of osteoporosis treatment initiation.
International Journal of Clinical Practice 08/2015; DOI:10.1111/ijcp.12676 · 2.54 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Statins were shown to down-regulate immune mechanisms activated in psoriasis. However, previous studies on their potential role in preventing psoriasis yielded conflicting results.
To assess the relationship between adherence with statins and the risk of psoriasis.
This retrospective cohort study included 205,820 health plan enrollees in Israel (mean age 55 years; 54.1% female) who initiated statin treatment from 1/1998 through 9/2009. Adherence with statins, measured by proportion of days covered (PDC) throughout the entire follow-up period (mean= 6.2 years). Diagnosis codes of psoriasis were given by a dermatologist or rheumatologist or at discharge from hospitalization RESULTS: During 1.28 million person-years (PY) of follow-up (median=5.74 years per person; IQR=3.78-8.36), a total of 5,615 psoriasis cases (incidence density= 4.4 per 1,000PY) were recorded. Compared with non-adherent patients (PDC<20%), patients covered with statins for 40%-59% of the time had a significantly (P<0.05) lower risk of psoriasis with hazard ratios (HRs) of 0.84 and 0.74 among males and females, respectively. Among more adherent patients (PDC≥80%), HRs were 0.88 (95%CI: 0.79-0.98) and 1.00 (0.90-1.11), respectively.
The results of the current study suggest that high and long-term adherence with statins is not associated with a meaningful reduction in the risk of psoriasis. This article is protected by copyright. All rights reserved.
This article is protected by copyright. All rights reserved.
British Journal of Dermatology 04/2015; DOI:10.1111/bjd.13850 · 4.10 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: 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 nonalcoholic 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.
A cross-sectional study using data 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=2,628).
The study population included 82,608 people (32.5% men, mean age 43.91±10.15 years). There was a significant positive dose-response 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).
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. This article is protected by copyright. All rights reserved.
This article is protected by copyright. All rights reserved.
Liver international: official journal of the International Association for the Study of the Liver 04/2015; 62. DOI:10.1111/liv.12842 · 4.41 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Aim: To describe the drug management of T2DM patients in a real life cohort with suboptimal HbA1c after treatment with metformin monotherapy. Methods: we performed a retrospective cohort analysis of computerized medical records after measuring an HbA1c >7% for the first time following at least 90 days on metformin therapy. Results: Among 7705 eligible patients, 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. Nonetheless, disease management programs aimed at improving guideline adherence and reducing inertia are still warranted. Summary points 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.
[Show abstract][Hide abstract] ABSTRACT: To assess the proportion of male versus female offspring of women diagnosed with SLE or RA, disorders in which female predominance is well known and PsA a disease in which female dominance is less established. The study population encompassed all females aged 16-46, who were members of the Maccabi Health Services (MHS) throughout the period of 2000-2011 and had at least one pregnancy. Data were retrieved from the computerized database of MHS, a 2-million enrollee health maintenance organization operating in Israel. The database was also used to collect data on patients with RA, SLE, and PsA. A total of 182,073 women had at least one indication of pregnancy during the study period. Among them, 546, 270, and 170 were diagnosed with RA, SLE, and PsA, respectively. The proportion of live-born males in 380,472 offspring of women free of these diseases was 51.5 % (95 % CI 51.4-51.7 %). The proportion (95 % CIs) of male offspring born to mothers diagnosed with of RA, SLE, and PsA were 46.3 % (42.3-50.3 %), 51.8 % (46.6-57.0 %), and 50.6 % (42.8-58.5 %), respectively. Our findings support the primary contribution of the hormonal phenotype rather than the genetic phenotype on autoimmunity. Neither patients with SLE or RA differ from the general population by the sex of their offspring.
Annals of the Rheumatic Diseases 11/2014; 73(Suppl 2). DOI:10.1007/s12026-014-8603-3 · 10.38 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The incidence of skin cancer, both melanoma and keratinocyte cancers (KC) is rising throughout the world, specifically squamous cell carcinomas(SCC) and basal cell carcinoma(BCC), being the most common of all cancers.
British Journal of Dermatology 06/2014; 172(1). DOI:10.1111/bjd.13213 · 4.10 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Previous assessments of the prevalence of resistant hypertension (RH) in uncontrolled blood pressure (BP) have ranged from 3% to 30%. Using real-world data, our aim was to estimate the prevalence of RH in patients belonging to the Maccabi Healthcare Services, a 2-million-member health organization in Israel. From 2010 to 2011, all hypertensive patients with ≥2 recorded BP measurements during a minimum period of 6 months were identified. Patients were considered uncontrolled if their most recent BP during the study period and their mean systolic BP or diastolic BP during a preceding period of ≥6months were systolic BP ≥140 mm Hg or diastolic BP ≥90 mm Hg, or systolic BP ≥130 mm Hg or diastolic BP ≥80 mm Hg in chronic kidney disease or diabetes mellitus. Uncontrolled patients taking diuretics and ≥2 antihypertensive therapy classes at their maximal recommended dose were regarded as resistant hypertensives. A total of 172 432 patients were eligible for the study. Uncontrolled BP was found in 35.9% (n=65 710). Overall, 2.2% of the uncontrolled patients (n=1487) were resistant hypertensives. Patients with RH were characterized by a significantly (P<0.01) older age, higher body mass index, and multicomorbidity (including dyslipidemia, diabetes mellitus, and impaired renal function) compared with patients with controlled hypertension receiving equivalent treatment. The results of this large population-based study indicate a substantially lower prevalence of RH than previously reported. Most patients with uncontrolled BP took less than the maximal recommended antihypertensive treatment.
[Show abstract][Hide abstract] 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.
JAMA The Journal of the American Medical Association 06/2014; 311(24). DOI:10.1001/jama.2014.6634 · 30.39 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background:
The dramatic increase in autism spectrum disorder (ASD) prevalence has been attributed to the broadening of diagnostic criteria, greater awareness, improved case finding methods, and the development of services for children with ASD. Diagnostic substitution has also been suggested as a reason for this increase, with several studies pointing to an increase in the diagnosis of ASD and a decrease in the diagnoses of intellectual disabilities, and other language and developmental disorders. However, to our knowledge, no studies have examined whether shifts in psychiatric diagnoses could contribute to the rise in ASD prevalence.
To describe the changes in diagnoses of autism and mental health disorders in children in Israel between 2003 and 2012, using data from psychiatrists in Maccabi Healthcare Services (MHS), a large healthcare organization in Israel.
A search of the MHS computerized databases was conducted for all diagnoses given to children (up to the age of 18) by psychiatrists from 2003 to 2012. Diagnoses were grouped by year and divided into ten broad categories, such as ASD, anxiety, and phobia. If a child received a diagnosis that fell into multiple categories, the diagnosis was listed in all relevant categories. However, if a child received the same type of diagnosis twice or more in a single year, the diagnosis was listed only once. The relative percentage change was calculated and chi square analysis was performed.
The total number of children diagnosed by psychiatrists in MHS increased from 1499 children in 2003 to 7327 in 2012. ASD accounted for 6.1% of all diagnoses in 2003, compared to 10.4% in 2012, representing a relative percentage increase of 69.2% (p<0.001). Statistically significant (p<0.01) relative increases between 2003 and 2012 were also found for behavior problems (60.7%), anxiety (58.6%) and ADHD (38.4%). A significant (p<0.001) decrease in the relative percentage between the same years was found for psychosis (58.5%), schizophrenia (40.8%) and depression (35.4%). Non-significant changes were found for phobia, obsessive compulsive disorder and bipolar diagnoses.
Results indicate a substantial shift in psychiatric case mix among children (up to the age of 18) between 2003 and 2012 in one of Israel’s largest healthcare organizations. ASD accounts for a growing proportion of all cases diagnosed by psychiatrists. While there was a relative increase also in behavior problems, anxiety and ADHD, there was a relative decrease in psychosis, schizophrenia, and depression. This shift may reflect psychiatric diagnosis substitution over time with an increasing number of children receiving an ASD diagnosis instead of other psychiatric diagnoses. Possible explanations for the shift in psychiatric case mix include increased awareness as well as a significant increase in services provided to children and adolescents with ASD.
2014 International Meeting for Autism Research; 05/2014
[Show abstract][Hide abstract] ABSTRACT: To investigate the prevalence and incidence of glaucoma in a large health maintenance organization (HMO) in Israel.
A population-based retrospective cohort study, conducted using electronic medical database.
Collected data included personal and medical characteristics.
Maccabi Healthcare Services, the second largest HMO in Israel insuring 2 million members and serving 25% of the population with a nationwide distribution.
Maccabi members from January 2003 to December 2010.
Prevalence and incidence of glaucoma according to the International Classification of Diseases, 9th revision, Clinical Modification diagnostic codes.
A total of 15,708 prevalent glaucoma patients were identified among active members of Maccabi in December 2010. A total of 15,332(97.6%) were 40 years or older, with a point prevalence of 2.2%. Prevalence of glaucoma was strongly associated with age, ranging from 0.28%at age 40-50 to 9.2% among elderly aged 80 or above. The 5 most prevalent diagnoses were open angle glaucoma (1.61%), exfoliation glaucoma (0.20%), unspecified glaucoma (0.17%), angle closure (0.11%), and normal tension glaucoma (0.06%). We identified 6,674 incident glaucoma patients diagnosed between 2003 and 2010. The observed incidence density rate among 40+ year old members was 1.84 (1.79-1.88) new cases per 1000 person years. Median age at diagnosis was 64 years old. The risk of glaucoma was similar between sexes up to age 70 years, and was significantly (P<0.01) higher in men in older ages.
Glaucoma affects nearly 10% of the elderly population in Maccabi with the highest risk of diagnoses at age 70 to 74. Since glaucoma leads to irreversible vision loss, the present estimates of morbidity should be of significant concern.
American Journal of Ophthalmology 05/2014; 158(2). DOI:10.1016/j.ajo.2014.04.026 · 4.02 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Introduction and Aims: Change in estimated GFR (eGFR) is frequently used to track CKD progression in clinical practice, trials and cohort studies
but its association with mortality has not been studied extensively.
Methods: Change in eGFR was estimated as % change from the first to last eGFR (CKD-EPI creatinine) in a 2-year baseline period. We
modeled the hazard ratios (HRs) of subsequent mortality as a spline function of % change in eGFR after adjusting for age,
sex, race, first eGFR, and co-morbid conditions. We used random effects meta-analyses to combine results stratified by first
baseline eGFR (<60 & ≥60) across studies.
Results: Mortality follow-up of 1,597,723 participants from 32 cohorts for a mean of 3.7 years after the 2-year baseline period showed
101,120 deaths for baseline eGFR <60 (n=395,394) and 57,472 deaths for baseline eGFR ≥60 (n=1,202,329). Change in eGFR had
a non-linear association with mortality (Figure for eGFR<60). A decline in eGFR was consistently associated with higher subsequent
mortality risk (adjusted HR for -30% vs. 0% change in eGFR were: 1.8 at eGFR <60; and 1.6 at eGFR ≥60; p<0.001). Similar results
were obtained for a 1- or 3-year change in eGFR. Hazards ratios were largely similar for those with eGFR ≥60 or when stratified
by ACR levels.
Conclusions: Declines in eGFR are strongly and consistently associated with subsequent risk of mortality adjusted for the first eGFR and
covariates. These findings support using smaller changes than -57% (equivalent to doubling of serum creatinine) in clinical
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[Show abstract][Hide abstract] ABSTRACT: The aim of this population-based study is to describe trends in the characteristics and treatment patterns of statin initiators over the first decade of the 21st century.
New statin use was studied retrospectively using the database of Maccabi Healthcare Services (MHS), a large Israeli health maintenance organization. Statin initiators were defined as MHS members aged ≥30 years who first purchased statins between 2000 and 2010. The starting dose was calculated in simvastatin equivalents based on the World Health Organization's daily defined dose index. Persistence was calculated as the percentage of days covered (PDC) with statins during the first year of therapy.
Statin initiation peaked in 2005 and decreased from 38.6 to 18.6 per 1,000 in the period 2005-2010. The average age at therapy initiation decreased from 58.9 (±12.0) to 54.5 (±11.7) years, and the average (SD) baseline low-density lipoprotein cholesterol (LDL-C) decreased from 4.2 (±1.1) to 4.0 (±0.9) mmol/l during the study period. Women were on average 3 years older than men at treatment initiation, with a higher baseline LDL-C. Among statin initiators, the prevalence of ischemic heart disease (IHD) decreased from 17.8 to 6.7 %, and diabetes prevalence increased from 8.6 to 15.7 %, peaking in 2008 (18.0 %). The PDC with statins ranged between 52.9 and 57.7 %. Simvastatin use at initiation increased from 27.5 % in 2000 to >90 % since 2002. Starting dose increased from 18.5 (±8.9) to 24.3 (±13.7) mg simvastatin equivalent.
Among the study population, statin initiators were increasingly characterized by a lower cardiovascular risk-namely, younger individuals without IHD and with a lower baseline LDL-C. These trends underscore the important shift towards statin initiation for primary prevention, as well as the need to balance between benefits and the potential side effect of statins.
European Journal of Clinical Pharmacology 01/2014; DOI:10.1007/s00228-013-1637-y · 2.70 Impact Factor