Place of Death for Israeli Cancer Patients Over a 20-Year Period: Reducing Hospital Deaths, but Barriers Remain.

BACKGROUND: Cancer remains a leading cause of mortality worldwide. While the main focus of palliative care (PC) is quality of life, the elements that comprise the quality of death are often overlooked. Dying at home, with home-hospice-care (HHC) support, rather than in-hospital, may increase patient satisfaction and decrease the use of invasive measures. We examined clinical and demographic characteristics associated with out-of-hospital death among patients with cancer, which serves as a proxy measure for HHC deaths. METHODS: Using death certification data from the Israel Central Bureau of Statistics, we analyzed 209,158 cancer deaths between 1998 and 2018 in Israel including demographic information, cause of death, and place of death (POD). A multiple logistic regression model was constructed to identify factors associated with out-of-hospital cancer deaths. RESULTS: Between 1998 and 2018, 69.1% of cancer deaths occurred in-hospital, and 30.8% out-of-hospital. Out-of-hospital deaths increased by 1% annually during the study period. Older patients and those dying of solid malignancies were more likely to die out-of-hospital (OR = 2.65, OR = 1.93, respectively). Likelihood of dying out-of-hospital varied with area of residency; patients living in the Southern district were more likely than those in the Jerusalem district to die out-of-hospital (OR = 2.37). CONCLUSION: The proportion of cancer deaths occurring out-of-hospital increased during the study period. We identified clinical and demographic factors associated with POD. Differences between geographical areas probably stem from disparity in the distribution of PC services and highlight the need for increasing access to primary EOL care. However, differences in age and tumor type probably reflect cultural changes and suggest focusing on educating patients, families, and physicians on the benefits of PC.

An Assessment of the Completeness and Timeliness of the Israel National Cancer Registry.

BACKGROUND: The Israel National Cancer Registry (INCR) was established in 1960. Reporting has been mandatory since 1982. All neoplasms of uncertain/unknown behavior, in situ and invasive malignancies (excluding basal and squamous cell carcinomas of the skin), and benign neoplasms of the brain and central nervous system (CNS) are reportable. OBJECTIVES: To assess completeness and timeliness of the INCR for cases diagnosed or treated in 2005. METHODS: Abstractors identified cases of in situ and invasive malignancies and tumors of benign and uncertain behavior of the brain and CNS diagnosed or treated in 2005 in the files of medical records departments, pathology and cytology laboratories, and oncology and hematology institutes in 39 Israeli medical facilities. Cases were linked to the INCR database by national identity number. Duplicate cases, and those found to be non-reportable were excluded from analysis. Completeness was calculated as the percent of reportable cases identified by the survey that were present in the registry. Timeliness was calculated as the percent of reportable cases diagnosed in 2005, which were incorporated into the registry prior to 31 December 2007. RESULTS: The INCR's completeness is estimated at 93.7% for all reportable diseases, 96.8% for invasive solid tumors, and 88.0% for hematopoietic tumors. Incident cases for the calendar year 2005 were less likely to be present in the registry database than those diagnosed prior to 2005. CONCLUSIONS: Completeness and timeliness of the INCR are high and meet international guidelines. Fully automated reporting will likely improve the quality and timeliness of INCR data.

Uterine cancer in Jewish Israeli BRCA1/2 mutation carriers.

BACKGROUND: BRCA1/2 mutation carriers have an increased risk of developing ovarian cancer, leading to the recommendation of risk-reducing salpingo-oophorectomy (RRSO) at 35-40 years of age. The role, if any, that BRCA mutations play in conferring uterine cancer risk, is unresolved. METHOD: Jewish Israeli women, carriers of one of the predominant Jewish mutations in BRCA1/2 from 1998 to 2016, were recruited. Cancer diagnoses were determined through the Israeli National Cancer Registry. Uterine cancer risk was assessed by computing the standardized incidence ratio of observed-to-expected number of cases, using the exact 2-sided P value of Poisson count. RESULTS: Overall, 2627 eligible mutation carriers were recruited from 1998 to 2016, 2312 (88%) of whom were Ashkenazi Jews (1463 BRCA1, 1154 BRCA2 mutation carriers, 10 double mutation carriers). Among these participants, 1310 underwent RRSO without hysterectomy at a mean (± standard deviation) age of 43.6 years (± 4.4 years). During 32,774 women-years of follow up, 14 women developed uterine cancer, and the observed-to-expected rate of all histological subtypes was 3.98 (95% confidence interval [CI], 2.17-6.67; P < .001). For serous papillary (n = 5), the observed-to-expected ratio was 14.29 (95% CI, 4.64-33.34; P < .001), and for sarcoma (n = 4) it was 37.74 (95% CI, 10.28-96.62). These rates were also higher than those detected in a group of 1844 age- and ethnicity-matched women (53% with breast cancer). CONCLUSION: Israeli BRCA1 or BRCA2 mutation carriers are at an increased risk for developing uterine cancer, especially serous papillary and sarcoma. These elevated risks of uterine cancer should be discussed with BRCA carriers.

Deliveries following fertility preservation by ovarian tissue cryopreservation without autotransplantation-what should be expected?

OBJECTIVE: To evaluate the delivery rate and to characterize patients following ovarian tissue cryopreservation (OTCP) who did not undergo auto-transplantation. METHODS AND MATERIALS: All consecutive cancer patients admitted to our IVF unit, from January 2004 to December 2015, who underwent OTCP for the purpose of fertility preservation without autotransplantation were analyzed. The cohort included 338 patients and was linked to the National Live Birth registry of the Israel Ministry of Health in order to determine whether the women delivered following the cancer diagnosis. MAIN OUTCOME MEASURES: Delivery rate following OTCP without autotransplantation. RESULTS: During 6.4 years of follow-up, 30% of the patients delivered, with no differences in gravity, age at first diagnosis of cancer, type of malignancy, or the prevalence of relapse of malignancy between those who delivered and those who did not. Moreover, in multivariate analysis, those undergoing OTCP before the age of 30 and those suffering from breast cancer had significantly higher odds to conceive and deliver following cancer treatment without the need of autotransplantation. CONCLUSIONS: Further studies are required to elucidate the appropriate subgroup of patients with breast cancer under the age of 30 years, who will need OTCP. This information might aid both fertility specialists' counseling and their oncological patients in pursuing the appropriate fertility preservation strategy.

Cancer surveillance in northern Africa, and central and western Asia: challenges and strategies in support of developing cancer registries.

The Global Initiative for Cancer Registry Development partnership, led by the International Agency for Research on Cancer (IARC), was established in response to an overwhelming need for high-quality cancer incidence data from low-income and middle-income countries. The IARC Regional Hub for cancer registration in North Africa, Central and West Asia was founded in 2013 to support capacity building for cancer registration in each of the countries in this region. In this Series paper, we advocate the necessity for tailored approaches to cancer registration given the rapidly changing cancer landscape for this region, and the challenges faced at a national level in developing data systems to help support this process given present disparities in resources and health infrastructure. In addition, we provide an overview of the status of cancer surveillance and activities country-by-country, documenting tailored approaches that are informing local cancer-control policy, and potentially curbing the growing cancer burden across the region.

Disease management in the treatment of patients with chronic heart failure who have universal access to health care: a randomized controlled trial.

BACKGROUND: The efficacy of disease management programs in improving the outcome of heart failure patients remains uncertain and may vary across health systems. This study explores whether a countrywide disease management program is superior to usual care in reducing adverse health outcomes and improving well-being among community-dwelling adult patients with moderate-to-severe chronic heart failure who have universal access to advanced health-care services and technologies. METHODS: In this multicenter open-label trial, 1,360 patients recruited after hospitalization for heart failure exacerbation (38%) or from the community (62%) were randomly assigned to either disease management or usual care. Disease management, delivered by multi-disciplinary teams, included coordination of care, patient education, monitoring disease symptoms and patient adherence to medication regimen, titration of drug therapy, and home tele-monitoring of body weight, blood pressure and heart rate. Patients assigned to usual care were treated by primary care practitioners and consultant cardiologists. The primary composite endpoint was the time elapsed till first hospital admission for heart failure exacerbation or death from any cause. Secondary endpoints included the number of all hospital admissions, health-related quality of life and depression during follow-up. Intention-to-treat comparisons between treatments were adjusted for baseline patient data and study center. RESULTS: During the follow-up, 388 (56.9%) patients assigned to disease management and 387 (57.1%) assigned to usual care had a primary endpoint event. The median (range) time elapsed until the primary endpoint event or end of study was 2.0 (0-5.0) years among patients assigned to disease management, and 1.8 (0-5.0) years among patients assigned to usual care (adjusted hazard ratio, 0.908; 95% confidence interval, 0.788 to 1.047). Hospital admissions were mostly (70%) unrelated to heart failure. Patients assigned to disease management had a better health-related quality of life and a lower depression score during follow-up. CONCLUSIONS: This comprehensive disease management intervention was not superior to usual care with respect to the primary composite endpoint, but it improved health-related quality of life and depression. A disease-centered approach may not suffice to make a significant impact on hospital admissions and mortality in patients with chronic heart failure who have universal access to health care. CLINICAL TRIAL REGISTRATION: Clinicaltrials.gov identifier: NCT00533013 . Trial registration date: 9 August 2007. Initial protocol release date: 20 September 2007.

Time Trends in the Incidence and Mortality of Ovarian Cancer in Ireland, Northern Ireland, and Israel, 1994-2013.

OBJECTIVES: The aims of this study were to compare time trends in ovarian cancer incidence and mortality in populations with (1) similar genetics but different health care systems (Ireland and Northern Ireland [NI]) and (2)different genetics but similar health care system (Israeli Jews and Arabs) and to interpret the results. METHODS: Age-standardized rates of ovarian cancer incidence and mortality for 1994-2013 in the 3 countries were obtained from national cancer registries and national statistics. Time trends in incidence, mortality, and incidence-to-mortality ratio were assessed by linear regression models applied to each country and between populations (Ireland-NI, Ireland-Israeli Jews, Israeli Jews-Arabs). Joinpoint analysis was used to calculate the annual percentage change (APC). RESULTS: Ovarian cancer incidence and mortality rates in 1994 were similar in the countries studied. Thereafter a reduction in incidence and mortality was observed in Ireland (incidence APC1994-2013 = -0.75%, P < 0.05; mortality APC1994-2013 = -0.67%, P < 0.05), NI (incidence APC1998-2013 = -1.5%, P < 0.05; mortality APC2005-2013 = -3.8%, P < 0.05), and Israeli Jews (incidence APC1994-2013 = -2.2%, P < 0.05; mortality APC1994-2013 = -1.2%, P < 0.05). Trends in Israeli Arabs remained stable. Significant incidence trend differences between Ireland and Israeli Jews (P = 0.009) and between Israeli Jews and Arabs (P = 0.004) were observed. The only significant trend difference for mortality was between Israeli Jews and Arabs (P = 0.038). Incidence-to-mortality ratios showed stable trends in all groups except for Israeli Jews (APC1994-2013 = -1.0%, P < 0.05). CONCLUSIONS: Time trends in ovarian cancer incidence (decreasing) and mortality (decreasing) were similar in Ireland, NI, and Israeli Jews, following global trends, with a more prominent incidence decline in Israeli Jews. Decreasing mortality trends are driven by falling incidence in the countries studied rather than improved survival.

Using Israel's National Cancer Registry Database to Track Progress in the War against Cancer: A Challenge for Health Services.

BACKGROUND: The number of cancer survivors has been increasing worldwide and is now approximately 32.6 million and growing. Cancer survivors present a challenge to health care providers because of their higher susceptibility to long-term health outcomes related to their primary disease and treatment. OBJECTIVES: To report on the number of cancer survivors and incident cancer cases in the period 1960-2009 in Israel, in order to provide data on the scope of the challenge Israel's health care funds face. METHODS: The Israel National Cancer Registry (INCR) database was used to identify new cancer cases diagnosed during the period 1960-2009. Lifetable analysis was used to assess changes in cumulative survival and population prevalence of cancer survivors throughout the 50 year study period. RESULTS: Almost 600,000 invasive cancer cases were diagnosed during the period 1960-2009 (overall absolute survival rate 54%). Within this time period, the number of new patients diagnosed with cancer increased fivefold and that of cancer survivors ninefold. The absolute survival of cancer patients and the prevalence of cancer survivors in the general population significantly increased with time from 34% and 0.5%, respectively (1960-1969), to 62% and 1.9%, respectively (2000-2009). Cumulative absolute survival for 5, 10 and 15 years following diagnosis increased with time as well. CONCLUSIONS: The INCR database is useful to assess progress in the war against cancer. The growing numbers of cancer survivors in Israel present a challenge to the national health and social services system.

Application of the double kernel density approach to the analysis of cancer incidence in a major metropolitan area.

RATIONALE: Although cancer is a main cause of human morbidity worldwide, relatively small numbers of new cancer cases are recorded annually in single urban areas. This makes the association between cancer morbidity and environmental risk factors, such as ambient air pollution, difficult to detect using traditional methods of analysis based on age standardized rates and zonal estimates. STUDY GOAL: The present study investigates the association between air pollution and cancer morbidity in the Greater Haifa Metropolitan Area in Israel by comparing two analytical techniques: the traditional zonal approach and more recently developed Double Kernel Density (DKD) tools. While the first approach uses age adjusted Standardized Incidence Ratios (SIRs) for small census areas, the second approach estimates the areal density of cancer cases, normalized by the areal density of background population in which cancer events occurred. Both analyses control for several potential confounders, including air pollution, proximities to main industrial facilities and socio-demographic attributes. RESULTS: Air pollution variables and distances to industrial facilities emerged as statistically significant predictors of lung and NHL cancer morbidity in the DKD-based models (p<0.05) but not in the models based on SIRs estimates (p>0.2). CONCLUSION: DKD models appear to be a more sensitive tool for assessing potential environmental risks than traditional SIR-based models, because DKD estimates do not depend on a priory geographic delineations of statistical zones and produce a smooth and continuous disease 'risk surface' covering the entire study area. We suggest using the DKD method in similar studies of the effect of ambient air pollution on chronic morbidity, especially in cases in which the number of statistical areas available for aggregation and comparison is small and recorded morbidity events are relatively rare.

The Use of National Cancer Registry Data for Breast Cancer Family History Assessment in Premenopausal Women.

Background: Population-based cancer registries are the best source of information to measure cancer burden. However, little is done to use this information for individual cancer risk assessment. In this study, we aimed at identifying women at high risk of breast and ovarian cancer using data on family history of cancer from the Israel national cancer registry. Methods: We used the family history assessment tool (FHAT) to score all females, 26 to 45 years of age, in a 2.6-million-member health provider in Israel (Maccabi Healthcare Services). Data on breast, ovarian, prostate, and pancreatic cancer history among the participants and their parents (identified using the national census) were retrieved from the national cancer registry. These data were used to calculate individual FHAT scores. Results: A total of 377,931 eligible women were included in the analysis. A relevant family history of cancer was detected in 20,386 (5.4%), with FHAT scores ranging from 1 to 16. FHAT score was higher in older women and among those with a history of breast cancer. Among women aged 35-39, an FHAT score of 10 or above was associated with an OR of 15.23 (95%CI: 7.41-28.19) for breast cancer compared to women with an FHAT of 0. Conclusions: Using individual-level data from national cancer registries may assist in detecting women with a relevant family history of cancer.

Physician specialty is associated with adherence to treatment guidelines for acute otitis media in children.

AIM: To identify physician and visit characteristics affecting adherence to guidelines recommending delayed antibiotic therapy for acute otitis media (AOM). METHODS: We used physician visit data from an Israeli health maintenance organization to identify children ages 0-15 diagnosed with AOM. We defined early antibiotic treatment as purchase, within 3 days of diagnosis, of antibiotics prescribed by the diagnosing physician. We considered the effect of physician specialty (paediatrician, otolaryngologist, and family physician), day of the week, setting (urgent care/clinic) and clinic location (peripheral/central) on the rate of early treatment. RESULTS: Proportion of cases receiving early treatment dropped from 2002 to 2009 in cases treated by otolaryngologists (47-36%) and paediatricians (46-42%) and increased in cases treated by family physicians (43-50%). Treatment rate was higher in cases treated on weekends than on weekdays (48% vs. 44%), in urgent care as compared to clinic settings (51% vs. 44%), and in children living in peripheral as compared to central areas (52% vs. 38%). CONCLUSIONS: Successful implementation of delayed treatment of otitis media guidelines requires addressing factors associated with increased early treatment rates.

Occupational Exposure to Nonionizing Radiation and Risk for Malignancy in Young Adults.

INTRODUCTION: Nonionizing radiation (NIR) is considered "possibly carcinogenic to humans," and therefore, exposure of young military personnel raises concerns regarding increased risk for cancer. The aim of our study was to compare the cancer incidence in exposed and nonexposed populations in order to gain better understanding of their risk. MATERIALS AND METHODS: A longitudinal retrospective cohort study, between 2009 and 2018, was conducted. Israel Defense Forces (IDF) aerial defense units service members, with NIR exposure (range of 2-300 GHz, below the International Commission of Non-Ionizing Radiation Protection guidelines), were compared with a similar sociodemographic group of service members without NIR exposure. Both groups were followed for cancer incidence (all-cause and specific malignancies). Kaplan-Meier analysis of cancer-free survival and univariate and multivariable logistic regressions for possible confounders and risk factors were performed. This analysis was repeated on a matched 1:1 control group. RESULTS: Exposure and comparison groups included 3,825 and 11,049 individuals, respectively. Forty-one cases diagnosed with cancer were identified during the follow-up time (mean 4.8 [±2.7] years), 13 (0.34%) of which were reported in the exposure group, and 28 (0.25%) were reported in the comparison group. The odds ratio (OR) for cancer incidence in the exposure vs. control groups was 1.34 (95%CI, 0.70-2.60), P-value = 0.3807. The results remained unchanged after adjustment for sex, age at enrollment, service length, socioeconomic status, and military occupation (adjOR = 1.38 [95%CI, 0.67-2.82], P = 0.3818). CONCLUSIONS: Our study did not find an increased short-term risk for cancer in young adults exposed to NIR radiation as compared with unexposed young adults.

Coexistence of malignancies in pemphigus vulgaris.

Pemphigus vulgaris (PV) is a rare autoimmune intraepidermal bullous disease. PV has a major effect on morbidity as well as quality of life. There is sparse literature regarding the association between pemphigus vulgaris (PV) and comorbid malignancies. In this study we aimed to assess the risk of malignancy in a cohort of patients with PV and characterize PV-associated malignancies. Data were collected from two tertiary referral centers between the years 2008 and 2019 and compared with the national cancer registry. Of 164 patients with PV, 19 were diagnosed with malignancy: seven prior to PV diagnosis and 12 after. All cancers, solid and hematological, displayed higher incidences compared to the general population (p <0.001). In conclusion, we demonstrated higher rates of malignancies among patients with PV than in the general population. These observations suggest the need for careful assessment and follow up of patients with PV, given the possibility of associated malignancies.

Construction of a multisite DataLink using electronic health records for the identification, surveillance, prevention, and management of diabetes mellitus: the SUPREME-DM project.

INTRODUCTION: Electronic health record (EHR) data enhance opportunities for conducting surveillance of diabetes. The objective of this study was to identify the number of people with diabetes from a diabetes DataLink developed as part of the SUPREME-DM (SUrveillance, PREvention, and ManagEment of Diabetes Mellitus) project, a consortium of 11 integrated health systems that use comprehensive EHR data for research. METHODS: We identified all members of 11 health care systems who had any enrollment from January 2005 through December 2009. For these members, we searched inpatient and outpatient diagnosis codes, laboratory test results, and pharmaceutical dispensings from January 2000 through December 2009 to create indicator variables that could potentially identify a person with diabetes. Using this information, we estimated the number of people with diabetes and among them, the number of incident cases, defined as indication of diabetes after at least 2 years of continuous health system enrollment. RESULTS: The 11 health systems contributed 15,765,529 unique members, of whom 1,085,947 (6.9%) met 1 or more study criteria for diabetes. The nonstandardized proportion meeting study criteria for diabetes ranged from 4.2% to 12.4% across sites. Most members with diabetes (88%) met multiple criteria. Of the members with diabetes, 428,349 (39.4%) were incident cases. CONCLUSION: The SUPREME-DM DataLink is a unique resource that provides an opportunity to conduct comparative effectiveness research, epidemiologic surveillance including longitudinal analyses, and population-based care management studies of people with diabetes. It also provides a useful data source for pragmatic clinical trials of prevention or treatment interventions.

Increased incidence with improved survival of gynecologic carcinosarcoma: A population-based study.

OBJECTIVE: To evaluate trends in the incidence and survival of gynecologic carcinosarcoma over the last 35 years and to explore ethnic disparities. STUDY DESIGN: Using the Israeli National Cancer Registry database, all cases of gynecologic carcinosarcoma were included (1980-2014). Age at diagnosis, patient's ethnicity and anatomical site were extracted. Age-standardized incidence rates (ASRs) were calculated for 3 time periods (1980-1994, 1995-2004 and 2005-2014). Relative survival was calculated using the Pohar-Perme method. RESULTS: Overall, 935 cases of gynecologic carcinosarcomas were diagnosed during 1980-2014. The most common gynecologic anatomical site was the uterus (83.4%). Most cases (66%) were diagnosed at ages 60-80, with median age of 69 years. There was a steady increase in ASRs from 5.6 to 8.2 per million women. Throughout 1980-1994 and 2005-2014, ASRs were significantly higher in the Jewish compared to the Arab population (5.8 vs. 3.1, p = 0.02 and 8.5 vs. 5.2, p = 0.002, respectively). Relative survival rates increased throughout the study period. No significant differences were noted in relative survival between the Jewish and Arab populations (p = 0.18). CONCLUSION: The incidence of gynecologic carcinosarcoma increased significantly from 1980 through 2014. Nevertheless, survival rates increased during this time, with no difference in survival between the Jewish and Arab populations.

A COVID-19 call center for healthcare providers: dealing with rapidly evolving health policy guidelines.

BACKGROUND: Communication between health authorities and healthcare providers is an essential element of the response to public health emergencies. Although call centers can facilitate such communication, no published reports describing their outcomes exist. In advance of the expected COVID-19 outbreak in Israel, the Israel Center for Disease Control established a call center dedicated to queries from healthcare professionals. METHODS: The call center operated from February 5, 2020 (week 6) to May 14, 2020 (week 20). Data on calls received, including date and time, caller characteristics, questions and responses were recorded in a database designed for this purpose. The volume, sources and content of queries were analyzed. RESULTS: In 15 weeks of operation, the call center responded to 6623 calls. The daily number of calls ranged from 1 to 371 (mean 79.8, median 40), peaking on week 12, 2 weeks prior to a peak in new COVID-19 cases. Callers were predominantly physicians (62.4%), nurses (18.7%) and administrators (4.4%). Most worked in primary care clinics (74.2%) or hospitals (8.7%). Among physicians, 42.3% were family physicians or internists, and 10.0% were pediatricians. The issues most commonly addressed were home quarantine (21.6%), criteria for suspected cases (20.6%), and SARS-CoV2 testing (14.1%). Twenty-five percent of questions involved requests for clarifications of MOH guidelines regarding travel restrictions, clinic management, triage of symptomatic patients, routine medical and dental care, recommended precautions for health care workers with preexisting medical conditions, and other matters. A total of 119 queries were not resolved on the basis of existing guidelines and were referred to MOH headquarters. CONCLUSIONS: This is the first report of a call center established to serve the needs of healthcare providers seeking guidance on COVID-19 management, and to facilitate communication of providers' concerns to the central health authority. Our work indicates that a central call center for healthcare providers can facilitate the development, implementation and amendment of guidelines and should be an integral element of the early response to public health emergencies. Real-time analysis of the call data may reveal important trends requiring prompt attention.

Use of hormone replacement therapy, 1998-2007: sustained impact of the Women's Health Initiative findings.

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.

Trends in the incidence of primary brain, central nervous system and intracranial tumors in Israel, 1990-2015.

BACKGROUND: The association between cellphone technology and brain, central nervous system (CNS) and intracranial tumors is unclear. Analysis of trends in incidence of such tumors for periods during which cellphone use increased dramatically may add relevant information. Herein we describe secular trends in the incidence of primary tumors of the brain and CNS from 1990 to 2015 in Israel, a period during which cellphone technology became extremely prevalent in Israel. METHODS: All cases of primary brain, CNS and intracranial tumors (excluding lymphomas) diagnosed in Israel from 1990 to 2015 were identified in the Israel National Cancer Registry database and categorized by behavior (malignant; benign/uncertain behavior) and histologic type. Annual age-standardized incidence rates by sex and population group (Jews; Arabs) were computed, and the annual percent changes and 95% confidence intervals per category were calculated using Joinpoint software. RESULTS: Over 26 years (1990-2015) no significant changes in the incidence of malignant brain, CNS and intracranial tumors were observed, except for an increase in malignant glioma incidence in Jewish women up to 2008 and Arab men up to 2001, which levelled off in both subgroups thereafter. The incidence of benign/uncertain behavior brain, CNS and intracranial tumors increased in most population groups up to the mid-2000s, a trend mostly driven by changes in the incidence of meningioma, but either significantly decreased (Jews) or stabilized (Arabs) thereafter. CONCLUSIONS: Our findings are not consistent with a discernable effect of cellphone use patterns in Israel on incidence trends of brain, CNS and intracranial tumors.

Second Primary Cancers After Primary Breast Cancer Diagnosis in Israeli Women, 1992 to 2006.

PURPOSE: Improvements in early detection and treatment have resulted in improved long-term survival from breast cancer, which increases the likelihood of the occurrence of second primary cancers. We calculated the risk of second primary cancers among Israeli women receiving a first primary breast cancer diagnosis. METHODS: By using data from the Israel National Cancer Registry, we identified 46,090 women with invasive breast cancer diagnosed between 1990 and 2006 and non-breast primary cancers diagnosed subsequent to breast cancer diagnosis. We used life table analysis to calculate the risk of a second primary cancer and calculated standardized incidence ratios (SIRs) by using age-specific cancer risk in the general population of Israeli women as the standard and stratifying by diagnosis period (1992 to 1996, 1997 to 2001, 2002 to 2006) and age at diagnosis (< 50 and ≥ 50 years). RESULTS: The probability of a second malignancy was 3.6% within 5 years, 8.2% within 10 years, and 13.9% within 15 years. The SIR for any second non-breast primary cancer was 1.26 (95% CI, 1.23 to 1.30). Significantly increased risks of colorectal, uterine, lung, ovarian, and thyroid cancer and leukemia were observed for the full follow-up period, which persisted after excluding the first 6 months after index diagnosis, although increased leukemia and colorectal cancer risks were no longer statistically significant. Women younger than age 50 years at initial diagnosis had a greater excess risk than women age 50 years and older (SIR, 1.77 [95% CI, 1.63 to 1.91] and 1.20 [95% CI, 1.15 to 1.24], respectively). CONCLUSION: The findings likely reflect a combination of personal risk factors (genetics, hormonal therapy, environmental exposures) as well as the effects of the initial cancer treatment and are unlikely to be explained by enhanced surveillance alone.

Trends of Second Primary Malignancy in Patients with Thyroid Cancer: A Population-Based Cohort Study in Israel.

BACKGROUND: Thyroid cancer (TC) is the most common endocrine malignancy. TC patients have a good prognosis and a low disease-related mortality rate. Since such patients are often young, they may be at a higher risk for a second primary malignancy (SPM). This study sought to determine the incidence, risk, and types of SPM between 1980 and 2011, and to assess SPM trends over time among Israeli TC patients. METHODS: Data were derived from the Israel National Cancer Registry. Primary TC patients diagnosed during 1980-2009 were followed up for SPM incidence until December 31, 2011. Standardized incidence ratios (SIRs) of observed to expected SPM (based on the general population rates) were calculated using Poisson regression. Analyses were stratified by time period of initial TC diagnosis (1980-1995 and 1996-2009). RESULTS: A total of 11,538 TC patients were identified. After exclusion of 107 duplicate cases, records of 1032 patients with SPM were analyzed (an SPM incidence of 8.9%). SIRs for all-site SPMs were 1.23 [confidence interval 1.08-1.35] for males and 1.19 [confidence interval 1.10-1.27] for females. SIRs for tumors of the urinary system and prostate were significantly elevated in males, as were SIRs for tumors of the brain, urinary system, breast, and lung in females. Variables associated with increased risk of developing SPMs included a younger age at TC diagnosis, a shorter latency period, being born in Asia/Africa for both sexes, and being born in Israel for females. Compared with the general population, a subanalysis by TC diagnosis during 1980-1995 and 1996-2009 disclosed a higher SPM incidence for the latter time period in males and for both time periods, with a slightly higher SIR for the latter time period in females. CONCLUSIONS: The overall risk of SPM in Israeli TC patients was significantly greater for both sexes compared with the general population, thus identifying TC patients as a high-risk group and calling for caretakers to apply specific follow-up guidelines.