Varda Shalev

Decline in estimated glomerular filtration rate and subsequent risk of end-stage renal disease and mortality

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.

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

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.

Continuation of Statin Treatment and All-Cause Mortality: A Population-Based Cohort Study

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 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.

Long-term persistence with statin treatment in a not-for-profit health maintenance organization: a population-based retrospective cohort study in Israel.

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.

Kidney Failure Risk Projection for the Living Kidney Donor Candidate

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 persons 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.).

The epidemiology of diabetes in a large Israeli HMO.

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 HMOs 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.

Persistence with Statins and Onset of Rheumatoid Arthritis: A Population-Based Cohort Study

In a retrospective cohort study, Gabriel Chodick and colleagues find a significant association between persistence with statin therapy and reduced risk of developing rheumatoid arthritis, but only a modest decrease in risk of osteoarthritis.

A population based study of the epidemiology of Herpes Zoster and its complications

OBJECTIVES To assess the incidence of Herpes Zoster (HZ) and its complications in the Israeli general population and specifically in immune-compromised individuals, and to identify risk factors for developing HZ and post-herpetic neuralgia (PHN). METHODS A retrospective database search for newly diagnosed cases of HZ and of PHN during 2006-2010 was conducted using the comprehensive longitudinal database of Maccabi Health Services. Cox-proportional hazards models were used to assess associations between risk factors and HZ and PHN. RESULTS During 2006-2010 there were 28,977 newly diagnosed cases of HZ and 1508 newly diagnosed cases of PHN. Incidence density rate of HZ was 3.46 per 1000 person-years in the total population and 12.8 per 1000 person-years in immune-compromised patients. HZ and PHN incidence increased sharply with age. 12.4% and 3.1% of elderly HZ patients (≥ 65 years) developed PHN or ophthalmic complications, respectively. In multivariable analyses, HZ and PHN were associated with female sex, higher socioeconomic status, diabetes mellitus, cancer history, and HIV treatment. CONCLUSIONS Extrapolating to the entire Israeli population, we estimate over 24,000 new cases of HZ and 1250 new cases of PHN each year. Cost-effectiveness analysis should be performed to determine the threshold age for vaccination against HZ.

Barriers and success factors in health information technology: A practitioner's perspective

Abstract Healthcare information technology is a key factor in improving quality and reducing cost in healthcare, and yet, the successful implementation of health IT varies greatly among healthcare systems. A review of the health IT literature supplemented by an analysis of the experience of successful IT implementation in Maccabi Healthcare Services, reveals that, despite differences among countries, common barriers to implementation of health IT and common critical success factors can be identified. Barriers include lack of clear benefits, sufficient incentives and adequate support for clinicians as well as payer–provider relationships, marketplace competition and privacy legislation. Critical success factors are innovative leadership, integrated management and collaboration with the doctors based on concrete needs, benefits, incentives and support. Dilemmas for managers include proof of return on investment for health IT versus leadership and tough management decisions; the optimal balance in the tradeoff between market dynamics, competition and choice, and the value of an integrated system that can generate significant benefit to clinicians, patients and payers; and the appropriate balance between privacy and improved quality of care, including the reduction of clinical error.

Seasonality in Birth Weight: Review of Global Patterns and Potential Causes

Abstract Birth weight is the single most significant determinant of infant mortality and the chances of a newborn to experience healthy development. Low birth weight also appears to be related to higher risks of several important chronic conditions, such as ischemic heart disease, non-insulin-dependent diabetes, and cancer in adults. Thus factors that influence in utero growth and birth weight may have a serious effect on health outcomes many years later in life. Analysis of seasonal variations in birth weights may enable us to suggest specific factors that influence this measure. In this review we summarize the literature on seasonal variations in birth weight. Although causes of seasonal variation in developing regions are more clearly understood, it is not yet clear which factors affect apparent seasonal variation in birth weight in developed countries. In our analysis we observed a pattern of seasonal variations in developed countries that differed between low-, middle-, and high-latitude countries, and we suggest several mechanisms that may be responsible for this diversity. Namely, we suggest that in middle-latitude climates, the large annual temperature range may cause low birth weights during summer, whereas in high- and low-latitude regions variations in sunlight exposure between seasons may contribute to low birth weights apparent during winter. Identification of the suggested causal environmental factors may have public health implications in the development of primary prevention programs for low birth weight and macrosomia in developed countries.