Colorectal cancer screening at age 45 years in Israel: Cost-effectiveness and global implications.

BACKGROUND: Colorectal cancer (CRC) incidence at ages <50 years is increasing worldwide. Screening initiation was lowered to 45 years in the United States. The cost-effectiveness of initiating CRC screening at 45 years in Israel was assessed with the aim of informing national policy and addressing internationally relevant questions. METHODS: A validated CRC screening model was calibrated to Israeli data and examined annual fecal immunochemical testing (FIT) or colonoscopy every 10 years from 45 to 74 years (FIT45-74 or Colo45-74) versus from 50 to 74 years (FIT50-74 or Colo50-74). The addition of a fourth colonoscopy at 75 years was explored, subanalyses were performed by sex/ethnicity, and resource demands were estimated. RESULTS: FIT50-74 and Colo50-74 reduced CRC incidence by 57% and 70% and mortality by 70% and 77%, respectively, versus no screening, with greater absolute impact in Jews/Other versus Arabs but comparable relative impact. FIT45-74 further reduced CRC incidence and mortality by an absolute 3% and 2%, respectively. With Colo45-74 versus Colo50-74, CRC cases and deaths increased slightly as three colonoscopies per lifetime shifted to 5 years earlier but mean quality-adjusted life-years gained (QALYGs) per person increased. FIT45-74 and Colo45-74 cost 23,800-53,900 new Israeli shekels (NIS)/QALYG and 110,600-162,700 NIS/QALYG, with the lowest and highest values among Jewish/Other men and Arab women, respectively. A fourth lifetime colonoscopy cost 48,700 NIS/QALYG. Lowering FIT initiation to 45 years with modest participation required 19,300 additional colonoscopies in the first 3 years. CONCLUSIONS: Beginning CRC screening at 45 years in Israel is projected to yield modest clinical benefits at acceptable costs per QALYG. Despite different estimates by sex/ethnicity, a uniform national policy is favored. These findings can inform Israeli guidelines and serve as a case study internationally.

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.

Secondary cancer after meningioma diagnosis: an Israeli national study.

BACKGROUND: There are limited data on whether primary diagnosis of meningioma may be associated with development of secondary primary cancer (SPC). METHODS: All meningioma cases (ICD-O-3 morphology codes 9530/0-9539/3) diagnosed in Jewish Israelis ≥ 20 years 1990 through 2015 registered in the Israel National Cancer Registry (INCR) were retrieved. All subsequent cancers occurring more than 6 months after meningioma diagnosis were identified. Risk of secondary cancer (SPC) was compared to cancer risk in the general population through the calculation of standardized incidence ratios (SIRs) and excess absolute risks (EARs). SIRs were stratified by type of second cancer, sex, and age group. Cox regression models were used to estimate hazard ratios of developing SPC. RESULTS: Overall, 8044 meningioma cases were identified: mean age at diagnosis was 64.0 ± 14.1 years. Of these, 927 (11.5%) were diagnosed with SPC (SIR 1.6, 95% CI 1.5-1.7). SPC risk was elevated in men (SIR 1.6, 95% CI 1.5-1.9) and women (SIR 1.6, 95% CI 1.5-1.8) diagnosed with meningioma in univariable analyses. Cancers most commonly encountered in the studied population were breast (17.6%), colorectal (13.4%), lung (8.1%), prostate (5%), and bladder (4.6%) cancer. In multivariable analyses, 10+ year increment in age at meningioma diagnosis was significantly associated with higher risk for SPC in individuals diagnosed with meningioma between 20 and 64 years, with an inverse association in the older age group (65+ years). CONCLUSIONS: Meningioma diagnosis is associated with an increased risk for developing secondary cancers. This risk should be discussed with patients treated for meningioma.

Breast cancer survivors: physical and mental quality of life 10 years following diagnosis, a case-control study.

PURPOSE: Improvements in diagnosis and treatment of Breast Cancer (BC) have resulted in an increase in the life expectancy of survivors and in the importance of quality of life in BC survivorship care. The current study aimed to assess the Health-Related Quality Of Life (HRQOL) of BC survivors and to investigate the association of comorbidities with HRQOL compared to a group of women with no history of cancer. METHODS: Women were residents of the central district in Israel, the case group included 250 women diagnosed with BC between 1999 and 2003, with no prior cancer history and no evidence of disease after 8-12 years. The comparison group included 250 women with no cancer history, individually matched to cases by age and area of residence. Data were collected through in-person interviews, and HRQOL was assessed using the Short Form-36 (SF-36) questionnaire. Regression analyses were performed evaluating the influence of demographic, socioeconomic, lifestyle characteristics and comorbidities on physical and mental HRQOL. RESULTS: The physical and mental summary scores means, were 48.5 ± 11.1 and 49.2 ± 10.8 compared to 51.5 ± 10.2 and 50.9 ± 10.6, in BC survivors and the comparison group, respectively (p = 0.002 and p = 0.097). BC survivors and controls did not differ in number and type of comorbidities and for both groups a negative association was seen with HRQOL. Controlling for age, income, number of comorbidities, BMI and physical activity, BC survivor had decreased physical (b = -2.49, p = 0.001) and mental summary scores (b = -1.27, p = 0.18). CONCLUSION: HRQOL of BC survivors should gain more attention in the area of cancer care, especially when comorbidities are present.

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.

Rising Incidence of Lung Cancer in Arab Females, Jewish Females, and Arab Males from 1990 to 2014 in Israel.

BACKGROUND: Lung cancer is the most common cause of cancer-related death. OBJECTIVES: To identify changing patterns of lung cancer and its histologic subtypes among different population groups in Israel over a 25 year period. METHODS: Primary lung cancers, all types and all stages, diagnosed during 1990-2014 were recorded in the Israel National Cancer Registry database. Demographic information was retrieved from the National Population Register. Age-standardized rates for the different subgroups were calculated for each year. Joinpoint software was used to analyze trends in incidence. RESULTS: We identified 42,672 lung cancer cases. The most common histology was adenocarcinoma (34%), followed by squamous cell carcinoma (19%), large cell/not-otherwise-specified (19%), other histologies (15%), and small cell lung cancer (11%). The adenocarcinoma incidence rose from 25.7% to 48.2% during the examined period. Large cell/not-otherwise-specified incidence peaked around 2005-2006 and declined after. Lung cancer incidence increased significantly for the population overall and specifically in Arab females, followed by Jewish females and by Arab males. Adenocarcinoma and small cell lung cancer increased in Jewish females and in Arab males. A younger age of diagnosis was seen in Arab compared to Jewish patients. CONCLUSIONS: Jewish females and Arab males and females living in Israel demonstrated a constant increase in lung cancer incidence, mostly in adenocarcinoma and small cell lung cancer incidence. In addition, a younger age of diagnosis in Arabs was noted. Smoking reduction interventions and screening should be implemented in those populations.

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.

Increased Risk for Cancer in Young Patients with Severe Obstructive Sleep Apnea.

BACKGROUND: Several studies in animal models and human with obstructive sleep apnea syndrome (OSAS) demonstrated an increase in cancer aggressiveness and mortality. However, there is a need for further clinical evidence supporting a correlation between OSAS and cancer incidence. OBJECTIVES: To reveal whether OSAS presence and severity is correlated with cancer incidence in a large homogenous patients' cohort. METHODS: We analyzed a cohort of over 5,000 concurrently enrolled patients, age > 18, with suspected OSAS, from a tertiary medical academic center. Patients underwent whole night polysomnography, the gold standard diagnostic tool for OSAS, and were classified for severity according to the Apnea Hypopnea Index (AHI). Data on cancer incidence were obtained from the Israel National Cancer Registry. A multivariate Cox proportional-hazards analysis, adjusted for age, gender, and BMI, was performed to estimate the hazard-ratio of new cancer incidence. RESULTS: Among 5,243 subjects with a median follow-up of 5.9 years, 265 were diagnosed with cancer. The most prevalent cancers were prostate (14.7%), hematological (12.8%), urothelial (9.4%), colorectal (9%), and breast (8.3%). In subjects who were diagnosed at age below 45 years (n = 1,533), a high AHI (> 57/h) was significantly associated with cancer (HR 3.7, CI 1.12-12.45, p = 0.008). CONCLUSIONS: Patients younger than 45 with severe OSAS have a significantly higher all-type cancer incidence than the general population. These results should encourage clinicians to detect and diagnose young patients with suspected OSAS and to recommend cancer screening methods in this high-risk population.

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.

Primary prevention and screening practices among long-term breast cancer survivors.

PURPOSE: Parallel to increasing survival of breast cancer (BC) patients, a need has arisen to characterize the follow-up required to improve and maintain their health. Our study aimed to assess changes in lifestyle habits over time among the study population, compare compliance rates of selected primary and secondary prevention practices between long-term BC survivors and an age-matched comparison group, and identify factors associated with compliance to these practices. METHODS: The study population comprised 250 Israeli BC survivors, diagnosed with BC between 1999 and 2003, without evidence of disease after 8-12 years, and 250 women with no cancer history, individually matched to survivors by age and area of residence. Data collection and analysis were conducted during August 2012-June 2015 and included socio-demographic variables, lifestyle habits, health promotion by the family physician, and participation in screening procedures and prevention measures. RESULTS: Higher performance rates of mammography and colonoscopy among BC survivors were observed, as well as a greater likelihood of receiving an influenza vaccine and undergoing a bone mineral density scan (adjusted-ORs: 7.7, 1.48, 1.42, and 2.59, respectively) compared to controls. Factors identified with compliance to selected practices were age, higher levels of education and income, never smoking, and strenuous physical activity. The survivors adopted healthier lifestyles, which were similar to those of women who never had cancer. CONCLUSIONS: About 10 years after BC diagnosis, the survivors generally comply with primary and secondary prevention practices.

Incidence and epidemiology of non-Hodgkin lymphoma and risk of second malignancy among 22 466 survivors in Israel with 30 years of follow-up.

Previous studies have shown an increase risk of second malignancies after non-Hodgkin's lymphoma (NHL), which is probably related to a combination of factors including genetic predisposition, molecular background, host immunological status and therapy administered. Here, we determined the incidence of NHL and risk of second solid tumours and haematological malignancies among survivors of NHL diagnosed in Israel during 1980-2011. Data were collected from the records of the Israeli National Cancer Registry. The total cohort of 24 666 NHL-patients included 22 601 Jews and 2065 Arabs. Median age of diagnosis for Jews was 61.3 years and 48.2 for Arab patients. Of the Jews with NHL, 11 265 (50%) were of European-American origin, 5005 (22%) Asian or African and 6114 (27%) were born in Israel. Second cancers were recorded in 2010 NHL survivors, 1918 Jews and 92 Arabs, representing a rate of 8.5%, and 4.5% o, respectively. Second malignancies in all recorded sites were more frequent than in the general population, with a standardized incidence ratio (SIR) of 1.28 for Jewish men, 1.25 for Jewish women, 1.73 for Arab men and 1.98 for Arab women. This higher risk was even more pronounced for the 309 cases with secondary haematological malignancies (secondary haematological malignancies of 1.97, 1.81, 4.48 and 4.15, respectively). Our findings show that there is an increased risk of second malignancies occurring after diagnosis of NHL in Israel, particularly for haematological malignancies such as leukaemia and NHL. The differences we report in the incidence of NHL and the types of second malignancies occurring among Jews and Arabs suggest that ethnicity and genetic susceptibility may be important relevant risk factors. Copyright © 2016 John Wiley & Sons, Ltd.

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.

Diabetes, prostate cancer screening and risk of low- and high-grade prostate cancer: an 11 year historical population follow-up study of more than 1 million men.

AIMS/HYPOTHESIS: An inverse association has consistently been shown between diabetes and prostate cancer incidence. We investigated whether lower prostate cancer incidence among men with diabetes is attributable to lower detection due to prostate cancer screening patterns. METHODS: We studied a population-based historical cohort of 1,034,074 Israeli men aged 21-90 years, without a previous history of cancer. The cohort was followed-up from 2002 to 2012, according to diabetes morbidity, for frequency of prostate-specific antigen (PSA) testing, mean PSA values and detection of prostate cancer, after adjustment for age, ethnic origin, socioeconomic status and PSA testing. RESULTS: In January 2002, 74,756 men had prevalent diabetes. During the 11 year follow-up, 765,483 (74%) remained diabetes-free and 193,835 developed diabetes. Approximately 10% more PSA screening was performed in men with than without diabetes, but the rate of PSA positivity (>4 µg/l) was 20% lower in men with diabetes. PSA values were already significantly lower in men who developed diabetes than in those who did not, 3 years before diabetes diagnosis. Reduced prostate cancer risk was observed among men with incident diabetes only for low-moderate grade tumours (Gleason score 2-6: adjusted HR 0.83; 95% CI 0.77, 0.89). No association was observed for high-grade tumours (Gleason score 7-10: HR 0.99; 95% CI 0.88, 1.11). CONCLUSIONS/INTERPRETATION: Our findings suggest that diabetes comorbidity is a factor to be considered in prostate cancer screening strategies, and specifically in the interpretation of PSA levels. Furthermore, our demonstration of reduced incidence of low-moderate grade but not high-grade prostate cancer tumours among men with diabetes supports the possibility that low PSA levels, rather than lower tumour risk, explains the observed reduced incidence of prostate cancer in men with diabetes. TRIAL REGISTRATION: ClinicalTrials.gov NCT02072902.

Identification of health care needs of long-term breast cancer survivors among Israeli women.

PURPOSE: Improvement in treatment has extended survival of breast cancer patients. Our study aimed to characterize health service use among long-term breast cancer survivors in Israel in order to identify and address specific needs of this subpopulation. METHODS: The study population included 250 women diagnosed with breast cancer, 8-12 years prior to study initiation (cases), and 250 individually matched cancer-free controls. Participants were recruited from the second largest Israeli HMO, and data were collected through personal interviews. ORs and 95 % CIs were estimated using conditional logistic regression and generalized estimating equations. RESULTS: Greater use of health services was observed among cases, compared to an age-matched comparison group, expressed by more visits to family physicians and specialists, longer duration of visits, more requests for referrals, more frequent contact with emergency services, and hospitalizations. The study groups were similar regarding socioeconomic variables, current smoking and physical activity, BMI, and prevalence of reported morbidity. Although 80 % of cases defined the family physician as their main treating physician, half still considered their oncologist responsible for cancer follow-up. Only 14.4 and 10.4 % of cases and controls, respectively, reported receiving psychological support during the year preceding the interview. CONCLUSIONS: Further studies should assess the contribution of apprehension concerning health-related issues that still accompany breast cancer survivors, to the excess use of health services. Concern among family practitioners may contribute as well. In addition, our results emphasize the need to improve coordination between the disciplines of oncology and community medicine for the medical care of this group.

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.

2012 Provisional classification criteria for polymyalgia rheumatica: a European League Against Rheumatism/American College of Rheumatology collaborative initiative.

The objective of this study was to develop European League Against Rheumatism/American College of Rheumatology classification criteria for polymyalgia rheumatica (PMR). Candidate criteria were evaluated in a 6-month prospective cohort study of 125 patients with new-onset PMR and 169 non-PMR comparison subjects with conditions mimicking PMR. A scoring algorithm was developed based on morning stiffness >45 minutes (2 points), hip pain/limited range of motion (1 point), absence of rheumatoid factor and/or anti-citrullinated protein antibody (2 points), and absence of peripheral joint pain (1 point). A score ≥4 had 68% sensitivity and 78% specificity for discriminating all comparison subjects from PMR. The specificity was higher (88%) for discriminating shoulder conditions from PMR and lower (65%) for discriminating RA from PMR. Adding ultrasound, a score ≥5 had increased sensitivity to 66% and specificity to 81%. According to these provisional classification criteria, patients ≥50 years old presenting with bilateral shoulder pain, not better explained by an alternative pathology, can be classified as having PMR in the presence of morning stiffness >45 minutes, elevated C-reactive protein and/or erythrocyte sedimentation rate, and new hip pain. These criteria are not meant for diagnostic purposes.

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.