Nationwide Evaluation of Quality of Care Indicators for Individuals with Severe Mental Illness and Diabetes Mellitus, Following Israel's Mental Health Reform.

Diabetes Mellitus (DM) is more common among individuals with severe mental illness (SMI). We aimed to assess quality-of-care-indicators in individuals with SMI following the 2015 Israel's Mental-Health-reform. We analyzed yearly changes in 2015-2019 of quality-of-care-measures and intermediate-DM-outcomes, with adjustment for gender, age-group, and socioeconomic status (SES) and compared individuals with SMI to the general adult population. Adults with SMI had higher prevalences of DM (odds ratio (OR) = 1.64; 95% confidence intervals (CI): 1.61-1.67) and obesity (OR = 2.11; 95% CI: 2.08-2.13), compared to the general population. DM prevalence, DM control, and obesity rates increased over the years in this population. In 2019, HbA1c testing was marginally lower (OR = 0.88; 95% CI: 0.83-0.94) and uncontrolled DM (HbA1c > 9%) slightly more common among patients with SMI (OR = 1.22; 95% CI: 1.14-1.30), control worsened by decreasing SES. After adjustment, uncontrolled DM (adj. OR = 1.02; 95% CI: 0.96-1.09) was not associated with SMI. Cardio-metabolic morbidity among patients with SMI may be related to high prevalences of obesity and DM rather than poor DM control. Effective screening for metabolic diseases in this population and social reforms are required.

The heritability of weight gain in infancy: A population-based twin study.

BACKGROUND: Rapid weight gain during infancy is a strong predictor of childhood obesity and is affected by genetic and environmental factors. Identifying ages with low heritability will allow for targeted interventions that might be able to prevent the adverse effects of childhood obesity. OBJECTIVES: The objective of the study is to estimate the heritability of weight gain from birth to defined ages during infancy, as well as during 6-month periods from birth to 18 months of age. We address this by leveraging large-scale computerised anthropometric data from the state-run network of well-baby clinics in Israel. METHODS: We performed a population-based twin study. We extracted weight measurements recorded between birth to 24 months from well-baby clinics for 9388 twin pairs born in Israel between 2011 and 2015. The reported sexes of the twins were used as a proxy for their zygosity status. We estimated the heritability of the weight z-score change from birth to specific ages and during particular periods in infancy. To assess the validity of the results, we repeated the analysis in a sub-cohort of twin pairs with complete weight measurements. RESULTS: During the first 2 years of life, heritability was lowest for birthweight ( h 2 = 0.40 ± 0.11 ). Heritability for weight gain since birth was highest at 4 months ( h 2 = 0.87 ± 0.13 ), and then gradually decreased until age 18 months ( h 2 = 0.62 ± 0.13 ). Estimating the heritability in 6-month intervals from birth to 18 months, heritability was highest during the 6-12-month interval ( h 2 = 0.84 ± 0.14 ), and was substantially lower during the subsequent 12-18-month interval ( h 2 = 0.43 ± 0.16 ). CONCLUSIONS: Heritability of weight gain decreases substantially in the second year of life, suggesting that this period could be an appropriate time for interventions for infants who are at an increased risk of childhood obesity.

Prenatal and postnatal exposure to NO2 and rapid infant weight gain - A population-based cohort study.

BACKGROUND: Childhood overweight and obesity is a global public health problem. Rapid infant weight gain is predictive of childhood overweight. Studies found that exposure to ambient air pollution is associated with childhood overweight, and have linked prenatal exposure to air pollution with rapid infant weight gain. OBJECTIVES: To examine the association between prenatal and postnatal ambient NO2 exposure, a traffic-related marker, with rapid weight gain in infants. METHODS: We carried out a population-based historical cohort study using data from the Israeli national network of maternal and child health clinics. The study included 474,136 infants born at term with birthweight ≥2500 g in 2011-2019 in central Israel. Weekly averages of NO2 concentration throughout pregnancy (prenatal) and the first 4 weeks of life (postnatal) were assessed using an optimized dispersion model and were linked to geocoded home addresses. We modelled weight gain velocity throughout infancy using the SuperImposition by Translation and Rotation (SITAR) method, a mixed-effects nonlinear model specialized for modelling growth curves, and defined rapid weight gain as the highest velocity tertile. Distributed-lag models were used to assess critical periods of risk and to measure relative risks for rapid weight gain. Adjustments were made for socioeconomic status, population group, subdistrict, month and year of birth, and the alternate exposure period - prenatal or postnatal. RESULTS: The cumulative adjusted relative risk for rapid weight gain of NO2 exposure was 1.02 (95% confidence intereval [CI] 1.00, 1.04) for exposure throughout pregnancy and 1.02 (95% CI 1.01, 1.04) for exposure during the first four postnatal weeks per NO2 interquartile range increase (7.3 ppb). An examination of weekly associations revealed that the critical period of risk for the prenatal exposure was from mid-pregnancy to birth. CONCLUSIONS: Prenatal and postnatal exposures to higher concentrations of traffic-related air pollution are each independently associated with rapid infant weight gain, a risk factor for childhood overweight and obesity.

Postnatal exposure to ambient temperature and rapid weight gain among infants delivered at term gestations: a population-based cohort study.

BACKGROUND: The global prevalence of childhood obesity has risen dramatically recently. Previous studies found an association between rapid infant weight gain and childhood overweight. Evidence suggests that exposure to high ambient air temperatures during prenatal life and during adulthood is associated with birthweight and obesity respectively. OBJECTIVE: The objective of this study was to examine whether exposure to high ambient temperatures during infancy is associated with rapid infant weight gain in Israel. METHODS: This is a population-based historical cohort study using data from the Israeli national public network of maternal and child health clinics between 2008 and 2013. We assessed exposure to ambient temperature in the first year of life using a high-resolution hybrid spatio-temporal model and calculated annual mean and minimum temperatures for each infant based on daily mean and minimum temperatures at the community clinic location. We defined rapid infant weight gain as a World Health Organization weight z-score difference >0.67 between birthweight and weight at age one year. We estimated these associations using log-linear and general additive models and adjusted for population group, district, maternal age, parental education, parity, sex, gestational age, birthweight, calendar year and calendar month of birth. RESULTS: The study population included 217,310 singleton-term infants. Adjusted models demonstrated a positive association between ambient temperature exposure and rapid infant weight gain. Compared to the third quintile of minimum temperature, infants exposed to the first and second quintile had an adjusted relative risk of 0.98 (95% CI 0.96, 1.00) and 0.97 (95% CI 0.95, 0.98), respectively, while those exposed to the fourth and fifth quintiles had an adjusted relative risk of 1.06 (95% CI 1.04, 1.07) and 1.02 (95% CI 1.00, 1.04) respectively. The associations with mean temperature were similar but slightly weaker. CONCLUSIONS: Exposure to higher ambient temperatures, of emerging importance in the climate change era, is associated with rapid infant weight gain in Israel. Future studies should use additional exposure, covariate, and outcome data to analyse the nature and the source of this association in more detail.

Israeli COVID lockdowns mildly reduced overall use of preventive health services, but exacerbated some disparities.

BACKGROUND: During 2020, Israel experienced two COVID-19-related lockdowns that impacted the provision of primary and secondary preventive care. METHODS: We examined the month-by-month performance of selected preventive care services using data from Israel's national Quality Indicators in Community Healthcare program. Process of care measures included hemoglobin A1c (HbA1c) testing, cholesterol testing, colon cancer screening and mammography. Intermediate outcome measures included low-density lipoprotein control and HbA1c control. Measures were stratified by sex and by area-level socioeconomic position (SEP). Diabetes and mammography are presented in this abstract due to space limitations. RESULTS: Annual HbA1c testing among persons with diabetes decreased from 90.9% in 2019 to 88.0% in 2020. Performance of HbA1c tests during lockdown months was as low as half the usual amount. There were compensatory increases in testing during post-lockdown months that did not quite make up for the missed tests. In 2019, 9.0% of Israelis with diabetes had poor glycemic control (HbA1c ≥ 9.0); in 2020, it was 8.8%. In total, 4.5% fewer mammograms were performed in 2020 compared with 2019. Women in the lowest SEP level performed 10.4% fewer mammograms in 2020 than in 2019, while women in the highest SEP level performed 3.1% more mammograms. CONCLUSIONS: Prolonged COVID lockdowns in 2020 were associated with marked decreases in the performance of preventive health services during those months. Compensatory spikes following the end of lockdowns partly, but did not completely, make up for the missed care. COVID lockdowns may have exacerbated socioeconomic disparities in some preventive health services.

Childhood Cancer and the Risk of ESKD.

BACKGROUND: Increasing cancer incidence among children alongside improved treatments has resulted in a growing number of pediatric cancer survivors. Despite childhood cancer survivors' exposure to various factors that compromise kidney function, few studies have investigated the association between childhood cancer and future kidney disease. METHODS: To assess the risk of ESKD among childhood cancer survivors, we conducted a nationwide, population-based, retrospective cohort study that encompassed all Israeli adolescents evaluated for mandatory military service from 1967 to 1997. After obtaining detailed histories, we divided the cohort into three groups: participants without a history of tumors, those with a history of a benign tumor (nonmalignant tumor with functional impairment), and those with a history of malignancy (excluding kidney cancer). This database was linked to the Israeli ESKD registry to identify incident ESKD cases. We used Cox proportional hazards models to estimate the hazard ratio (HR) of ESKD. RESULTS: Of the 1,468,600 participants in the cohort, 1,444,345 had no history of tumors, 23,282 had a history of a benign tumor, and 973 had a history of malignancy. During a mean follow-up of 30.3 years, 2416 (0.2%) participants without a history of tumors developed ESKD. Although a history of benign tumors was not associated with an increased ESKD risk, participants with a history of malignancy exhibited a substantially elevated risk for ESKD compared with participants lacking a history of tumors, after controlling for age, sex, enrollment period, and paternal origin (adjusted HR, 3.2; 95% confidence interval, 1.3 to 7.7). CONCLUSIONS: Childhood cancer is associated with an increased risk for ESKD, suggesting the need for tighter and longer nephrological follow-up.

Holocaust Experience and Mortality Patterns: 4-Decade Follow-up in a Population-Based Cohort.

Research on mortality associated with exposure to the Holocaust is relevant for a better understanding of the effects of genocides on survivors. To our knowledge, previous studies have not investigated the long-term cause-specific mortality of Holocaust survivors. We compared mortality rates among Israelis born in European countries controlled by the Nazis during World War II with those among Israelis of European descent who did not have this exposure. Records of 22,671 people (45% women; 5,042 survivors) from the population-based Jerusalem Perinatal Study (1964-1976) were linked to the Israeli Population Registry, which was updated through 2016. Cox models were used for analysis, with 2-sided tests of statistical significance. Risk of all-cause mortality was higher among exposed women (hazard ratio (HR) = 1.15, 95% confidence interval (CI): 1.05, 1.27) than in unexposed women. No association was found between Holocaust exposure and male all-cause mortality. In both sexes, survivors had higher cancer-specific mortality (HR = 1.17 (95% CI: 1.01, 1.35) in women and HR = 1.14 (95% CI: 1.01, 1.28) in men). Exposed men also had excess mortality due to coronary heart disease (HR = 1.39, 95% CI: 1.09, 1.77) and lower mortality from other known causes combined (HR = 0.86, 95% CI: 0.75, 0.99). In summary, experiencing the Holocaust was associated with excess all-cause and cancer-specific mortality in women and cancer- and coronary heart disease-specific mortality in men.

Associations Between Prenatal Exposure to Air Pollution and Congenital Hypothyroidism.

Adequate thyroid hormone availability is required for normal brain development. Studies have found associations between prenatal exposure to air pollutants and thyroid hormones in pregnant women and newborns. We aimed to examine associations of trimester-specific residential exposure to common air pollutants with congenital hypothyroidism (CHT). All term infants born in Israel during 2009-2015 were eligible for inclusion. We used data on CHT from the national neonatal screening lab of Israel, and exposure data from spatiotemporal air pollution models. We used multivariable logistic regression models to estimate associations of exposures with CHT, adjusting for ethnicity, socioeconomic status, geographical area, conception season, conception year, gestational age, birth weight, and child sex. To assess residual confounding, we used postnatal exposures to the same pollutants as negative controls. The study population included 696,461 neonates. We found a positive association between third-trimester nitrogen oxide exposure and CHT (per interquartile-range change, odds ratio = 1.23, 95% confidence interval: 1.08, 1.41) and a similar association for nitrogen dioxide. There was no evidence of residual confounding or bias by correlation among exposure periods for these associations.

History of Childhood Kidney Disease and Risk of Adult End-Stage Renal Disease.

BACKGROUND: The long-term risk associated with childhood kidney disease that had not progressed to chronic kidney disease in childhood is unclear. We aimed to estimate the risk of future end-stage renal disease (ESRD) among adolescents who had normal renal function and a history of childhood kidney disease. METHODS: We conducted a nationwide, population-based, historical cohort study of 1,521,501 Israeli adolescents who were examined before compulsory military service in 1967 through 1997; data were linked to the Israeli ESRD registry. Kidney diseases in childhood included congenital anomalies of the kidney and urinary tract, pyelonephritis, and glomerular disease; all participants included in the primary analysis had normal renal function and no hypertension in adolescence. Cox proportional-hazards models were used to estimate the hazard ratio for ESRD associated with a history of childhood kidney disease. RESULTS: During 30 years of follow-up, ESRD developed in 2490 persons. A history of any childhood kidney disease was associated with a hazard ratio for ESRD of 4.19 (95% confidence interval [CI], 3.52 to 4.99). The associations between each diagnosis of kidney disease in childhood (congenital anomalies of the kidney and urinary tract, pyelonephritis, and glomerular disease) and the risk of ESRD in adulthood were similar in magnitude (multivariable-adjusted hazard ratios of 5.19 [95% CI, 3.41 to 7.90], 4.03 [95% CI, 3.16 to 5.14], and 3.85 [95% CI, 2.77 to 5.36], respectively). A history of kidney disease in childhood was associated with younger age at the onset of ESRD (hazard ratio for ESRD among adults <40 years of age, 10.40 [95% CI, 7.96 to 13.59]). CONCLUSIONS: A history of clinically evident kidney disease in childhood, even if renal function was apparently normal in adolescence, was associated with a significantly increased risk of ESRD, which suggests that kidney injury or structural abnormality in childhood has long-term consequences.

Socioeconomic Disparity Trends in Cancer Screening Among Women After Introduction of National Quality Indicators.

PURPOSE: Primary care physicians have an important role in encouraging adequate cancer screening. Disparities in cancer screening by socioeconomic status (SES) may affect presentation stage and cancer survival. This study aimed to examine whether breast, colorectal, and cervical cancer screening rates in women differed by SES and age, and whether screening rates and SES disparities changed after introduction of a primary care-based national quality indicator program. METHODS: This repeated cross-sectional study spanning 2002-2017 included all female Israeli residents in age ranges appropriate for each cancer screening assessed. SES was measured both as an individual-level variable based on exemption from copayments and as an area-level variable using census data. RESULTS: In 2017, the most recent year in the study period, screening rates among 1,529,233 women were highest for breast cancer (70.5%), followed by colorectal cancer (64.3%) and cervical cancer (49.6%). Women in the highest area-level SES were more likely to undergo cervical cancer screening compared with those in the lowest (odds ratio = 3.56; 99.9% CI, 3.47-3.65). Temporal trends showed that after introduction of quality indicators for breast and colorectal cancer screening in 2004 and 2005, respectively, rates of screening for these cancers increased, with greater reductions in disparities for the former. The quality indicator for cervical cancer screening was introduced in 2015, and no substantial changes have occurred yet for this screening. CONCLUSIONS: We found increased uptake and reduced socioeconomic disparities after introduction of cancer screening indicators. Recent introduction of a cervical cancer screening indicator may increase participation and reduce disparities, as has occurred for breast and colorectal cancer screening. These findings related to Israel's quality indicators program highlight the importance of primary care clinicians in increasing cancer screening rates to improve outcomes and reduce disparities.

Childhood risk factors for adulthood chronic kidney disease.

Chronic kidney disease (CKD) is a major public health challenge, affecting as much as 8 to 18% of the world population. Identifying childhood risk factors for future CKD may help clinicians make early diagnoses and initiation of preventive interventions for CKD and its attendant comorbidities as well as monitoring for complications. The purpose of this review is to describe childhood risk factors that may predict development of overt kidney disease later in life. Currently, there are multiple childhood risk factors associated with future onset and progression of CKD. These risk factors can be grouped into five categories: genetic factors (e.g., monogenic or risk alleles), perinatal factors (e.g., low birth weight and prematurity), childhood kidney diseases (e.g., congenital anomalies, glomerular diseases, and renal cystic ciliopathies), childhood onset of chronic conditions (e.g., cancer, diabetes, hypertension, dyslipidemia, and obesity), and different lifestyle factors (e.g., physical activity, diet, and factors related to socioeconomic status). The available published information suggests that the lifelong risk for CKD can be attributed to multiple factors that appear already during childhood. However, results are conflicting on the effects of childhood physical activity, diet, and dyslipidemia on future renal function. On the other hand, there is consistent evidence to support follow-up of high-risk groups.

Kidney failure risk in type 1 vs. type 2 childhood-onset diabetes mellitus.

BACKGROUND: Diabetic kidney disease (DKD) is becoming increasingly common among children. We aimed to estimate the risk of end-stage renal disease (ESKD) and mortality among adolescents with type 1 diabetes mellitus (T1DM) or type 2 diabetes mellitus (T2DM) and normal renal function compared with non-diabetics. We hypothesized that childhood onset T1DM vs. T2DM would be associated with a different risk profile for developing ESKD and its complications. METHODS: A nationwide, population-based, retrospective cohort study, including 1,500,522 adolescents examined for military service between 1967 and 1997, which were classified according to the presence and type of diabetes. Data were linked to the Israeli ESKD registry. Cox proportional-hazards models were used to estimate the hazard ratio (HR) for ESKD. RESULTS: At study enrolment, 1183 adolescents had T1DM and 196 had T2DM. ESKD developed in 2386 non-diabetic individuals (0.2%) compared with 72 individuals (6.1%) with T1DM and 8 individuals (4.1%) with T2DM. Participants with T1DM were younger at ESKD onset than participants with T2DM (median age, 36.0 vs. 40.5 years, P < 0.05). In a multivariate model adjusted for age, sex, paternal origin, enrollment year, BMI, and blood pressure, T1DM and T2DM were associated with HR of 36.4 (95% CI 28.3-46.9) and 19.3 (95% CI 9.6-38.8) for ESKD, respectively. Stratification according to sex, ethnicity, immigration, and socioeconomic status did not materially change the HR. During the follow-up period, mortality rates were higher in T2DM as compared with T1DM and controls (8.7 %, 2.2%, and 2.7% respectively). CONCLUSIONS: T1DM and T2DM in adolescents with normal renal function confer a significantly increased risk for ESKD. T1DM is associated with younger age at ESKD onset while T2DM is associated with higher mortality rate.

Associations of diet, physical activity and polycystic ovary syndrome in the Coronary Artery Risk Development in Young Adults Women's Study.

BACKGROUND: Current evidence supports the adoption of healthy diet and physical activity (PA) behaviors in patients with polycystic ovary syndrome (PCOS), given the positive effects of those behaviors on physical well-being. An improved understanding of the associations between diet and PA with PCOS is needed to ascertain whether tailored dietary and PA recommendations are needed for this population. Thus, we investigated the associations of diet and PA with PCOS and its isolated features. METHODS: Cross-sectional study. Of the 748 women who were included in this study from the Coronary Artery Risk Development in Young Adults (CARDIA) Women's Study, 40 were classified as having PCOS, 104 had isolated hyperandrogenism (HA) and 75 had isolated oligomenorrhea (OA). Dietary intake was measured using the CARDIA diet history questionnaire and diet quality was scored using the Alternative Healthy Eating Index 2010; a higher score indicated a better quality diet. Self-reported PA was measured using a validated interviewer-administered questionnaire. Polytomous logistic regression analyses examined the associations between diet and PA with PCOS, HA, and OA status (outcomes), adjusting for age, race, total energy intake, education, and/or body mass index. The threshold for statistical significance was set at p < 0.05. RESULTS: Mean age of the participants was 25.4 years (SD 3.6) and 46.8% of participants were Black women. There was little to no association of total energy intake, nutrients, diet quality, and PA with PCOS, HA or OA status. CONCLUSION: Energy intake, nutrient composition, diet quality, and PA were not associated with PCOS, supporting recent PCOS guidelines of using national recommendations for the general population to encourage health-promoting behaviors among women with PCOS. However, longitudinal studies evaluating changes in diet and physical activity in relation to the development and/or the progression of PCOS are needed to establish a causal association.

Birth Weight and Maternal Body Size as Determinants of Blood Pressure at Age 17: Results from the Jerusalem Perinatal Study Cohort.

OBJECTIVES: To investigate the effect of birth weight (BW) and maternal pre-pregnancy BMI (mBMI) on blood pressure (BP) in adolescence. METHODS: A Population-based cohort of 11,729 births in Jerusalem during 1974-1976, with archival data on maternal and birth characteristics was performed. Measurements at age 17 were assessed and linear regression models were used to evaluate the associations of birth characteristics with BP outcomes. RESULTS: BW was inversely associated with both systolic (SBP) and diastolic (DBP) BP at age 17 (SBP: B = - 0.829, p = 0.002; DBP: B = - 0.397, p = 0.033). The interaction term between BW and weight at age 17 was significant for DBP (p = 0.017) and pulse pressure (p = 0.005). mBMI yielded significant positive associations with BP, independent of BW. CONCLUSIONS FOR PRACTICE: Our findings indicate that there are at least two distinct pathways linking early life characteristics with subsequent BP: Intrauterine growth, as reflected by BW and other genetic or environmental factors, reflected by mBMI and maternal education, contribute to offspring adolescent BP. These results warrant replication in other birth cohorts and underline the need to explore specific mechanisms that account for these associations.

[ANTIBIOTIC USE IN COMMUNITY HEALTHCARE IN ISRAEL AS REFLECTED IN THE NATIONAL PROGRAM FOR QUALITY INDICATORS].

AIMS: We sought to evaluate the extent of overall and second-line systemic antibiotic use in the Israeli community, to compare them to international data and to monitor temporal trends. BACKGROUND: Antibiotic overuse is prevalent and has grave implications, primarily the emergence of resistant pathogens - an urgent public health concern worldwide. METHODS: The Israel National Program for Quality Indicators in Community Healthcare (QICH) obtains data from electronic medical records from the 4 health-plans, covering the entire civilian population. We assessed 2 quality indicators, compatible with those of the OECD: 1. Overall volume of antibiotics for systemic use dispensed. 2. Volume of second-line antibiotics as a proportion of all systemic antibiotics. Analysis was stratified by gender, age and socio-economic position (SEP). RESULTS: The volume of systemic antibiotics dispensed in 2016 was 20.76 DDD/1000 person/day, with second-line antibiotics comprising 22.0% of the total. These values have been stable since 2014, and are higher compared with the OECD averages (20.61 DDD/1000 person/day, and 17.02% in 2015). Both overall volume and the proportion of second-line antibiotics rose with age and were higher among women especially in the 20-40 years age bracket (overall volume of 23.98 DDD/1000 person/day, proportion of second-line antibiotics of 23.98% VS 17.41 and 19.17% in men). Higher overall use was observed among patients of low SEP. CONCLUSIONS: The observed volume of systemic antibiotics and the proportion of second-line antibiotics dispensed in the Israeli community were stable and high. Higher use was observed among older individuals, women and patients of low SEP. Our results call for the implementation of a national-level, community-based antibiotic stewardship program. QICH might serve to monitor such a program.

Mammographic breast density in recent and longer-standing ethiopian immigrants to israel.

High breast density is associated with an increased risk of breast cancer development. Little is known concerning ethnic variations in breast density and its relevant contributing factors. We aimed to study breast density among Ethiopian immigrants to Israel in comparison with Israeli-born women and to determine any effect on breast density of the length of residency in the immigrant population. Mammographic breast density using the BI-RADS system was estimated and compared between 77 women of Ethiopian origin who live in Israel and 177 Israeli-born controls. Logistic regression analysis was performed to estimate the odds ratios (OR) for high density (BI-RADS score ≥ 3) vs low density (BI-RADS score < 3) cases, comparing the 2 origin groups. Ethiopian-born women had a crude OR of 0.15 (95% CI: 0.08-0.26) for high breast density compared with Israeli-born women. Adjustments for various cofounders did not affect the results. Time since immigration to Israel seemed to modify the relationship, with a stronger association for women who immigrated within 2 years prior to mammography (OR:0.07, 95% CI: 0.03-0.17) as opposed to women with a longer residency stay in Israel (OR:0.23, 95% CI:0.10-0.50). Adjustments of various confounders did not alter these findings. Breast density in Ethiopian immigrants to Israel is significantly lower than that of Israeli-born controls. Our study suggests a positive association between time since immigration and breast density. Future studies are required to define the possible effects of dietary change on mammographic density following immigration.

[HADASSAH MEDICAL ORGANIZATION - A PIONEER IN POPULATION HEALTH].

INTRODUCTION: Population health is a term encompassing "the health outcomes of a group of individuals, including the distribution of such outcomes within the group." Only recently have hospitals viewed themselves as focal points for promoting health in a community, involving themselves with population health. Hadassah Medical Organization (HMO), however, has been in the business of population health since its founding. Its early programs, promoting and delivering nutritional support, maternal-child health and other services to the Yishuv's inhabitants, showed that the HMO defined its community broadly. Hospital care came later. The HMO was established together with the Hebrew University Israel's first School of Public Health and Community Medicine in the 1960's, contributing >1200 Israeli alumni, and exposing thousands of medical students to population health. The School's founders developed Community-Oriented Primary Care, aimed at assessing and addressing health determinants and outcomes at the community level implemented in many centers worldwide. Reaching beyond Israel's borders, the School has trained a global public health workforce through its International Masters in Public Health with >820 graduates from 92 countries. HMO's researchers have made important contributions in the fields of epidemiology, health economics and policy and population health methodology as well as hospital and community quality of care. This article reviews HMO's contribution to population health at local, municipal, national and international levels. We will demonstrate the unique circumstances in Hadassah, Jerusalem and Israel which have enabled world-class research and training in population health, identifying important contributions to policy and service provision, as well as addressing future population health challenges.

Grand multiparity and reproductive cancer in the Jerusalem Perinatal Study Cohort.

OBJECTIVES: Grand multiparity is associated with reduced mortality from reproductive cancers. We aimed to separate the components of mortality, by measuring incidence of and survival after reproductive cancer onset in grand multiparous compared to other parous women. STUDY DESIGN: We linked data from the population-based Jerusalem Perinatal Study Cohort, which included women aged 13-55 who delivered 1964-1976, with Israel's National Cancer Registry. We compared breast and gynecologic cancer risk and all-cause survival following a cancer diagnosis, among grand multiparae (GMPs = parity 5+, n = 8,246) versus women with parity 1-4 (n = 19,703), adjusting for reproductive and demographic variables. RESULTS: Grand multiparae were at significantly lower risk of breast cancer than others (adjusted hazard ratio (HRadj) = 0.62, 95 % confidence interval (CI) 0.54-0.71), after controlling for age at first birth, education, and other covariates. This reduction was greater among GMPs whose first birth occurred after age 30 (p-interaction = 0.0001) and for cancer occurring before age 50 years (p = 0.002). In contrast, GMPs were at greater risk of death than women with parity <5, following a breast cancer diagnosis (HRadj = 1.69, CI 1.39-2.1). Ovarian, uterine, and cervical cancer incidence did not differ between the groups, but survival was reduced for GMPs with uterine cancer (HRadj = 2.48, CI 1.22-5.03). CONCLUSION: Reduced reproductive cancer mortality reported among GMPs masks two opposing phenomena: decreased breast cancer risk and poorer survival after breast and uterine cancers. The latter unfavorable outcome suggests that tumors in GMPs may be particularly aggressive, having perhaps escaped protective mechanisms conferred by parity. This finding calls for heightened clinical attention in this group.