A historical cohort study with 27,754 individuals on the association between meat consumption and gastrointestinal tract and colorectal cancer incidence.

In order to explore the association between meat consumption and gastrointestinal/colorectal cancer (CRC) risk and to estimate the Israeli population attributable fraction (PAF), we conducted a collaborative historical cohort study using the individual participant data of seven nutritional studies from the past 6 decades. We included healthy adult men and women who underwent a nutritional interview. Dietary assessment data, using food-frequency or 24-h recall questionnaires, were harmonized. The study file was linked to the National Cancer and death registries. Among 27,754 participants, 1216 (4.4%) were diagnosed with gastrointestinal cancers and 839 (3.0%) with CRC by the end of 2016. Using meta-analysis methods applied to Cox proportional hazard models (adjusted for daily energy intake, sex, age, ethnic origin, education and smoking),100 g/day increments in beef, red meat and poultry consumption, and 50 g/day increment in processed meat consumption were associated with hazard ratios (HRs) and 95% confidence intervals of 1.46 (1.06-2.02), 1.15 (0.87-1.52), 1.06 (0.89-1.26), and 0.93 (0.76-1.12), respectively, for CRC. Similar results were obtained for gastrointestinal cancer, although red meat consumption reached statistical significance (HR = 1.27; 95%CI: 1.02-1.58). The PAFs associated with a reduction to a maximum of 50 g/day in the consumption of red meat were 2.7% (95%CI: -1.9 to 12.0) and 5.2% (0.3-13.9) for CRC and gastrointestinal cancers, respectively. Reduction of beef consumption to a maximum of 50 g/day will result in a CRC PAF reduction of 7.5% (0.7%-24.3%). While beef consumption was associated with gastrointestinal/CRC excess risk, poultry consumption was not. A substantial part of processed meat consumption in Israel is processed poultry, perhaps explaining the lack of association with CRC.

Methodology and challenges for harmonization of nutritional data from seven historical studies.

BACKGROUND: Collection of detailed dietary data is labor intensive and expensive, harmonization of existing data sets has been proposed as an effective tool for research questions in which individual studies are underpowered. METHODS: In this paper, we describe the methodology used to retrospectively harmonize nutritional data from multiple sources, based on the individual participant data of all available studies, which collected nutritional data in Israel between 1963 and 2014. This collaboration was established in order to study the association of red and processed meat with colorectal cancer. Two types of nutritional questionnaires, the Food Frequency Questionnaires (FFQ) and the 24-h dietary recall (24HR recall), and different food composition tables, were used by the participating studies. The main exposure of interest included type of meat (total meat, red meat, and poultry) and level of processing. RESULTS: A total of 29,560 Israeli men and women were enrolled. In studies using FFQ,the weighted mean intakes of total, red, processed meat, and poultry were 95, 27, 37 and 58 gr/day and 92, 25, 10, and 66 gr/day in studies using 24HR recall, respectively.. Despite several methodological challenges, we successfully harmonized nutritional data from the different studies. CONCLUSIONS: This paper emphasizes the significance and feasibility of harmonization of previously collected nutritional data, offering an opportunity to examine associations between a range of dietary exposures and the outcome of interest, while minimizing costs and time in epidemiological studies.

Self-reported physical activity properties and 20-year all-cause and cardiovascular mortality among community-dwelling older adults.

PURPOSE: Physical activity was previously associated with decreased mortality. Current guidelines recommend >150 min/week or >75 min/week of moderate or high-intensity exercise to maintain a healthy lifestyle; however, exercise properties most strongly associated with low mortality among the elderly may still be explored. METHODS: A total of 1210 community-dwelling older adults, from the third phase (1999-2004) of the Israel Study on Glucose Intolerance, Obesity, and Hypertension, were followed until 2016 and 2019 for cardiovascular and all-cause mortality, respectively. Physical activity properties were recorded and evaluated against all-cause and cardiovascular mortality. RESULTS: Mean age at baseline was 73 ± 7 years, with 638 (53%) females, and 585 (48%) reported habitual exercise. When compared to sedentary individuals, multivariable Cox regressions showed a significantly lower risk for all-cause mortality among currently active individuals [hazard ratio (HR) = 0.72, 95% confidence interval (CI): 0.59-0.88, P = .002], those engaging in light-moderate activity (HR = 0.72, 95% CI: 0.57-0.89, P = .003), those with diverse exercise types (HR = 0.59, 95% CI: 0.44-0.80, P = .001), more sessions/week (HR = 0.94, 95% CI: 0.92-0.97, P < .001), those meeting current exercise recommendations (HR = 0.79, 95% CI: 0.58-0.89, P = .03), those who engaged in walking (HR = 0.58, 95% CI: 0.45-0.76, P < .001), and swimming (HR = 0.66, 95% CI: 0.45-0.96, P = .03). Similar HRs were found for cardiovascular mortality, although a somewhat stronger protective association was observed for swimming (HR = 0.48, 95% CI: 0.24-0.95, P = .04) compared to a sedentary lifestyle. CONCLUSION: The study further supports current exercise guidelines among the elderly. It also underscores the importance of physical activity in older individuals while prioritizing a greater number of sessions/week in addition to the total duration, and highlights specific activity features associated with lower long-term mortality among older adults. Key message • What is already known on this topic - Physical activity was associated with a lower risk for mortality, although the specific properties and the preferred type of exercise among older adults are still debatable. • What this study adds - The study suggests the optimal activity characteristics in older adults while prioritizing activity sessions over time, light-moderate exercise over strenuous activity, diverse activity, and walking and swimming over other activities. • How this study might affect research, practice or policy - Future exercise guidelines should focus on increasing activity sessions throughout the week and not on the cumulative time to maximize the effect on mortality.

Subfertility, use of fertility treatments and BRCA mutation status and the risk of ovarian cancer.

PURPOSE: The objective of the study is to evaluate the possible association between history of subfertility, fertility treatments, BRCA mutations and the risk of ovarian cancer. METHODS: This Israeli National Case-Control study included 1269 consecutive ovarian cancer cases and 2111 individually matched healthy controls. All participants were interviewed and molecular analysis of BRCA mutations were performed to 896 cases. The main outcome measure was reported history of subfertility and exposure to fertility treatments. RESULTS: The rate of reported subfertility was 15.1% and 14.3% in ovarian cancer cases and controls, respectively. However, subfertility was more prevalent in cases with borderline ovarian cancer (but not for invasive ovarian cancer cases) than controls. Multivariate conditional logistic regression revealed that the risk of borderline ovarian cancer was elevated in both women treated for subfertility and those that were not treated for subfertility, (OR = 1.74; 95% CI 0.9-3.36 and OR = 1.79; 95% CI 0.98-3.26, respectively). In non-carriers of BRCA1/2 mutations, fertility treatments were associated with a decreased risk of invasive ovarian cancer while a significant increased risk of borderline ovarian cancer was observed (OR = 2.92, 95%CI 1.67-5.10). CONCLUSIONS: Reported subfertility and exposure to fertility treatments were associated with borderline but not with invasive ovarian tumors. This association was more prominent in women who are non-carriers of a BRCA mutation.

[PREDICTION MODEL FOR ASSESSING PHYSICAL FITNESS IN CARDIAC PATIENTS].

AIMS: To develop and validate a readily-available tool for the evaluation of the fitness of cardiac patients. BACKGROUND: Physical fitness is an important factor in the tertiary prevention for cardiac patients. METHODS: In this cross-sectional study, 154 cardiac patients: 119 men and 35 women, mean age 63.1±11.2 years, entering the cardiac-rehabilitation program at the Sheba Medical Center, gave informed consent and completed a 24-hour recall physical activity questionnaire. Information on BMI, medication use and on their performance on a symptom-free limited treadmill test, i.e. measured estimated VO2 (ml/kg/min) and resting heart rate (bpm), were obtained from the medical chart. RESULTS: A linear-regression equation for predicting the measured estimated VO2 includes the overall physical activity index calculated from the physical activity questionnaire, sex, age, BMI, type of coronary heart disease (acute myocardial infarction, coronary artery bypass graft, percutaneous coronary intervention), duration of illness, resting heart rate, use of beta-blockers and level of education. The correlation coefficient between measured VO2 values and calculated values is r=0.6. Upon categorizing patients to high and low physical fitness according to the VO2 median value, the validity of the equation was found to be good: sensitivity=61.2%, specificity=65.2%, positive predictive value=68.4%, negative predictive value=57.7%. CONCLUSIONS: The prediction equation for assessing VO2 in cardiac patients is a simple, inexpensive tool, which may be used for monitoring changes in the patients' physical fitness. It may assist the physician in following a cardiac patient's response to physical activity recommendations and improving fitness when the ergometric stress-test availability is low.

Childhood Exposure to Low to Moderate Doses of Ionizing Radiation and the Risk of Vascular Diseases.

In the Tinea Capitis Study (Israel, 1966-2011), we assessed the association between childhood exposure to low to moderate doses of ionizing radiation (IR) to the head and neck and the development of vascular diseases (ischemic heart disease, carotid artery stenosis, and stroke) in adulthood. The study included 17,734 individuals from the Tinea Capitis cohort (7,408 irradiated in childhood and 10,326 nonirradiated), insured by Israel's largest health provider. Individual dosimetry was estimated based on measurements made on a head phantom and original treatment records. The mean doses were 1.5, 0.09, 0.78, and 0.017 Gy to brain, thyroid, salivary gland, and breast, respectively. Data on vascular diseases was abstracted from computerized medical records. Using Poisson regressions, we examined the association of radiation with morbidity. Any vascular disease was reported for 2,221 individuals. Adjusted for age, sex, socioeconomic status, smoking, hypertension, and diabetes, exposure to IR increased the risk of developing any vascular diseases (relative risk (RR) = 1.19, 95% confidence interval (CI): 1.09, 1.29), stroke (RR = 1.35, 1.20, 1.53), carotid artery stenosis (RR = 1.32, 1.06, 1.64), and ischemic heart disease (RR = 1.12, 1.01, 1.26). The risk of developing vascular diseases was positively associated with dose and inversely associated with age at exposure. In conclusion, the results indicate that early exposure to low to moderate doses of IR increases the risk of cerebro- and cardiovascular impairments.

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.

The association between insulin sensitivity indices, ECG findings and mortality: a 40-year cohort study.

BACKGROUND: Type 2 Diabetes is a major risk factor for cardiovascular (CV) mortality. Insulin resistance can be evaluated non-invasively by insulin sensitivity indices (ISI) such as the Mcauley index (MCAi), which is a function of the fasting insulin and triglycerides. Currently, the association between ISIs and ECG findings and all-cause and CV mortality is still not established in a large scale and heterogeneous population. METHOD: In a prospective study of the Israel cohort on Glucose Intolerance, Obesity and Hypertension (GOH) second phase (1979-1982) 1830 men and women were followed until December-2016 for CV-mortality and December-2019 for all-cause mortality. ECGs were recorded and OGTTs performed during baseline. ISIs were categorized into quartiles and evaluated against ECG findings and all-cause and CV-mortality. RESULTS: Mean age at baseline was 52.0 ± 8.1 years, and 75 (15.2%) and 47 (25.3%) participants in the upper quartiles (Q2-4) and the lower quartile (Q1) of the MCAi, presented with Ischemic changes on ECG respectively (p = 0.02). Multivariable analysis showed higher odds for ECG ischemic changes, for individuals in Q1-MCAi (adjusted-OR = 1.7, 95% CI 1.02-2.8), compared with Q2-4-MCAi, which attenuated when excluding individuals with diabetes (adjusted-OR = 1.6, 95% CI 0.9-2.7, p = 0.09). Median follow up for all-cause and for cardiovascular mortality was 31 years and 37 years, respectively. Cox proportional-hazards regression showed an increased risk for all-cause mortality for individuals in Q1-MCAi (HR = 1.2, 95% CI 1.02-1.3) as well as an increased risk for CV-mortality (HR = 1.4, 95%CI 1.1-1.8) compared with Q2-4-MCAi. Individuals in Q4-Ln Homeostatic model assessment- Insulin Resistance (HOMA-IR) and Q1- Quantitative Insulin Sensitivity Check Index (QUICKI) also presented with increased risk for all-cause-mortality (HR = 1.2, 95%CI 1.04-1.4; and HR = 1.2, 95% CI 1.04-1.4, respectively). Other ISIs did not show significant associations with CV-mortality. CONCLUSION: Higher insulin-resistance, according to the MCAi, associated with ECG-changes, and with greater risk for all-cause and CV-mortality over a 40-year follow-up. The MCAi may be considered as an early predictive and prognostic biomarker for CV-morbidity and mortality in adults.

Oncology Treatments during the COVID-19 Pandemic in Israel: the ONCOR Study.

BACKGROUND: The increased susceptibility of cancer patients to coronavirus disease-2019 (COVID-19) infections and complications calls for special precautions while treating cancer patients during COVID-19 pandemics. Thus, oncology departments have had to implement a wide array of prevention measures. OBJECTIVES: To address issues associated with cancer care during the COVID-19 pandemic and to assess the implementation of measures aimed at containment of COVID-19 diffusion while allowing continuation of quality cancer care. METHODS: A national survey among oncology departments in Israel was conducted between 12 April 2020 and 14 April 2020. Eighteen heads of hospital-based oncology departments completed a self-report questionnaire regarding their institute's preparedness for treatment of cancer patients during the COVID-19 pandemic. RESULTS: In this national survey, prevention measures against COVID-19 spread were taken prior to patients' arrival and at arrival or while staying in the departments. Most participants (78-89%) reported using a quick triage of patients and caregivers prior to their entrance to the oncology units, limiting the entrance of caregivers, and reducing unnecessary visits to the clinic. Switching to oral therapies rather than intravenous ones when possible was considered by 82% and shortage in personal protective equipment was reported by five (28%) heads of oncology departments. Some differences between large and small/medium sized medical centers were observed regarding issues related to COVID-19 containment measures and changes in treatment. CONCLUSIONS: Oncology departments in Israel were able to prepare and adapt their services to guidelines and requirements related to the COVID-19 pandemic with little harm to their treatment capacity.

Fifteen-year survival of invasive epithelial ovarian cancer in women with BRCA1/2 mutations - the National Israeli Study of Ovarian Cancer.

OBJECTIVE: Compare 5, 10 and 15 year survival in invasive epithelial ovarian cancer, between patients with and without BRCA1/2 germ line mutation in a nonselective group of patients diagnosed during 1994-99. METHODS: The analysis was based on 779 Jewish patients: 229 carriers to the Ashkenazi Jewish founder mutations in BRCA1 (185delAG; 5382insC) and BRCA2 (6174delT); and 550 non-carriers. Clinical characteristics were abstracted from the patients' medical records and vital status was updated through the National Population Registry up to 11/2015. The Kaplan-Meier method, log-rank tests, and Cox-regression model were used for survival analyses. RESULTS: By the end of the follow-up period, (range 1-20 years), 629 (80.7%) deaths occurred. While considerably higher survival was observed during the first 5 years from diagnosis among carriers compared to non-carriers (46.7% vs. 36.2%, p = 0.0004), the survival rates at 15 years were 22.3% vs. 21.8% respectively (p = 0.04). The age-adjusted hazard ratio for all-cause mortality of carriers versus non-carriers was 0.74 (95%CI 0.60-0.91) in the first 5 years. For women who survived 5 and 10 years, the age-adjusted hazard ratios for mortality during 5 additional years, of carriers compared to non-carriers, were 1.38 (95%CI 0.93-2.04) and 1.08 (95%CI 0.61-1.92), respectively. CONCLUSION: The results of this study, with up to 20 years follow-up, support studies with shorter follow-up that suggested that the advantage in survival observed among BRCA1/2 carriers during the first 5 years decreases over time. Clinically, this may have implications for follow-up and therapy, especially of new agents that are particularly effective in BRCA carriers.

Lessons learned from the 1-hour post-load glucose level during OGTT: Current screening recommendations for dysglycaemia should be revised.

This perspective covers a novel area of research describing the inadequacies of current approaches for diagnosing dysglycaemia and proposes that the 1-hour post-load glucose level during the 75-g oral glucose tolerance test may serve as a novel biomarker to detect dysglycaemia earlier than currently recommended screening criteria for glucose disorders. Considerable evidence suggests that a 1-hour post-load plasma glucose value ≥155 mg/dl (8.6 mmol/L) may identify individuals with reduced ß-cell function prior to progressing to prediabetes and diabetes and is highly predictive of those likely to progress to diabetes more than the HbA1c or 2-hour post-load glucose values. An elevated 1-hour post-load glucose level was a better predictor of type 2 diabetes than isolated 2-hour post-load levels in Indian, Japanese, and Israeli and Nordic populations. Furthermore, epidemiological studies have shown that a 1-hour PG ≥155 mg/dl (8.6 mmol/L) predicted progression to diabetes as well as increased risk for microvascular disease and mortality when the 2-hour level was <140 mg/dl (7.8 mmol/L). The risk of myocardial infarction or fatal ischemic heart disease was also greater among subjects with elevated 1-hour glucose levels as were risks of retinopathy and peripheral vascular complications in a Swedish cohort. The authors believe that the considerable evidence base supports redefining current screening and diagnostic recommendations with the 1-hour post-load level. Measurement of the 1-hour PG level would increase the likelihood of identifying a larger, high-risk group with the additional practical advantage of potentially replacing the conventional 2-hour oral glucose tolerance test making it more acceptable in a clinical setting.

Cancer risk among Holocaust survivors in Israel-A nationwide study.

BACKGROUND: Holocaust survivors during World War II were exposed to various factors that are associated with cancer risk. The objective of this study was to determine whether Holocaust survivors had an increased risk for developing cancer. METHODS: The study population included 152,622 survivors. The main analysis was based on a comparison between individuals who were entitled to compensation for suffering persecution during the war and individuals who were denied such compensation. A complementary analysis compared survivors who were born in countries governed by Nazi Germany with survivors born in nonoccupied countries. A Cox proportional hazards model was used, with the time at risk of cancer development starting on either January 1, 1960, or the date of immigration to the date of cancer diagnosis or death or the date of last follow-up (December 31, 2006). RESULTS: Cancer was diagnosed in 22.2% of those who were granted compensation versus 16% of those who were denied compensation (P < .0001). Adjusting for birth cohort, sex, country of origin, and period of immigration, both analyses revealed significant increased risks of developing cancer in those who were exposed. For those who were granted versus denied compensation, the hazard ratios were 1.06 (P < .001) for all sites, 1.12 (P = .07) for colorectal cancer, and 1.37 (P = .008) for lung cancer. For those born in occupied countries versus nonoccupied countries, the hazard ratios were 1.08 (P < .001), 1.08 (P = .003), and 1.12 (P = .02), respectively. CONCLUSIONS: The current results, based on a large cohort of Holocaust survivors who were exposed to a variety of severe deprivations, add to the conflicting and sparse knowledge on this issue and support the notion that this group has a small but consistent increase in cancer development. Cancer 2017;123:3335-45. © 2017 American Cancer Society.

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.

Healthy Lifestyle Pattern is Protective Against 30-Yr Cancer Incidence in Men and Women: A Cohort Study.

OBJECTIVES: Investigate associations of healthier behaviors with 30-yr cancer incidence. SUBJECTS/METHODS: In 1982, 632 healthy men and women (ages 40-70) were interviewed for nutritional habits using a Food Frequency Questionnaire and a 24-h physical activity questionnaire. Blood pressure, weight, and height were measured, and blood was drawn for biochemical profiles. Thirteen and four subjects were excluded due to cancer diagnosis ≤1 yr from recruitment and extreme values of reported total daily calorie intake, respectively. RESULTS: During a mean follow-up of 24.2 yr, 146 cancer incident patients (23.7%) were documented. Total cancer risk was 38% lower in the medium vegetable intake tertile [adjusted hazards ratio (HR) = 0.62, 95%confidence interval (CI): 0.40-0.95], and 66% higher in the medium fruit intake tertile (adjusted HR = 1.66, 95%CI: 1.08-2.55) compared to the lowest tertile. The risk of gastrointestinal cancers was 3 times greater for the highest, compared to the lowest, dairy consumption tertile (HR = 3.06, 95%CI: 1.01-9.23). "Healthy lifestyle" (normal BMI, never smoked, consuming high levels of dietary fiber and vegetables, and more physically active) reduced overall cancer risk (adjusted HR = 0.63, 95%CI: 0.44-0.91) as compared to the rest of the cohort. CONCLUSIONS: Our findings reinforce the importance of lifestyle-related factors, which are relatively low-cost and may contribute to reduction in the burden of malignant diseases.

Occupational exposure to metals and risk of meningioma: a multinational case-control study.

The aim of the study was to examine associations between occupational exposure to metals and meningioma risk in the international INTEROCC study. INTEROCC is a seven-country population-based case-control study including 1906 adult meningioma cases and 5565 population controls. Incident cases were recruited between 2000 and 2004. A detailed occupational history was completed and job titles were coded into standard international occupational classifications. Estimates of mean workday exposure to individual metals and to welding fumes were assigned based on a job-exposure-matrix. Adjusted odds ratios (ORs) and 95 % confidence intervals (CIs) were estimated using conditional logistic regression. Although more controls than cases were ever exposed to metals (14 vs. 11 %, respectively), cases had higher median cumulative exposure levels. The ORs for ever vs. never exposure to any metal and to individual metals were mostly greater than 1.0, with the strongest association for exposure to iron (OR 1.26, 95 % CI 1.0-1.58). In women, an increased OR of 1.70 (95 % CI 1.0-2.89) was seen for ever vs never exposure to iron (OR in men 1.19, 95 % CI 0.91-1.54), with positive trends in relation with both cumulative and duration of exposure. These results remained after consideration of other occupational metal or chemical co-exposures. In conclusion, an apparent positive association between occupational exposure to iron and meningioma risk was observed, particularly among women. Considering the fact that meningioma is a hormone dependent tumor, the hypothesis that an interaction between iron and estrogen metabolism may be a potential mechanism for a carcinogenic effect of iron should be further investigated.

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.

Dysglycemia and long-term mortality: observations from the Israel study of glucose intolerance, obesity and hypertension.

BACKGROUND: We describe the relationship between dysglycemia and long-term mortality and elucidate the relationship between blood glucose levels during an oral glucose tolerance test (OGTT) and haemoglobin A1 (HbA1) and mortality. METHODS: A cohort of 1410 individuals was followed for 33 years since 1980. Fasting and post-OGTT glucose parameters were used to categorize the cohort according to baseline glycemic status. RESULTS: The mortality rate increased from 43% in normoglycemic individuals to 53.3, 61.7, 72.9 and 88.0% in those with impaired fasting glucose (IFG), impaired glucose tolerance (IGT), IFG/IGT and diabetes, respectively. The highest mortality rate, compared with the normoglycemic category, was observed in individuals with IFG/IGT and diabetes according to a Cox proportional hazard model (HR = 1.38, 95%CI 1.10-1.74 and HR = 2.14, 95%CI 1.70-2.70, respectively), followed by individuals with IGT and IFG, but this did not reach statistical significance. We speculate that the IFG group may represent a mixture of individuals en route from normal to the next two categories as well as another cohort whose glucose levels are stably set at the upper reaches of the normal distribution. Significant differences were found between 1 and 2 h glucose values (p < 0.001). Fasting, 60 and 120 min glucose values were positively associated with increasing HbA1 quintiles (p < 0.05). The mean HbA1 was significantly higher in those who died (p = 0.01). The highest mortality (58.8%) was observed in the upper HbA1 quintile that was also associated with the highest prevalence of the metabolic syndrome (17.2%). CONCLUSIONS: This study shows a continuous relationship between the severity of dysglycemia and long-term mortality and should promote the early recognition of prediabetes. The 1 h post-load glucose level was continuously associated with increasing HbA1 concentrations and may therefore serve as an early marker for abnormalities in glucose tolerance. An elevated 1 h post-load glucose level may potentially identify at-risk individuals well before the traditional 2 h glucose value.

Sex and ethnic-origin specific BMI cut points improve prediction of 40-year mortality: the Israel GOH study.

BACKGROUND: Although obesity has been associated with a higher risk for premature death, the sex and ethnic-origin specific body mass index (BMI) levels that are associated with increased mortality are controversial. We investigated the 40-year cumulative all-cause mortality, in relation to the BMI in adult life, among men and women originating from Yemen, Europe/America, Middle East and North Africa, using sex and ethnic-origin specific BMI cut points. METHODS: A random stratified cohort (n = 5710) was sampled from the central population registry and followed since 1969 for vital status. Weight, height and blood pressure were measured, and smoking status was recorded at baseline. BMI was analysed according to conventional categories and according to sex and ethnic-origin specific quintiles. RESULTS: Elevated and significant mortality hazard ratios (HRs) of 1.21 [95% confidence interval (CI) 1.00-1.45] for women and 1.22 (95%CI 1.03-1.44) for men were found for the highest origin-specific BMI quintile. In men, the lowest ethnic-origin specific quintile was also significantly associated with increased mortality (HR of 1.22 95% CI 1.03-1.45), adjusting for age, smoking and blood pressure. Obesity was associated with mortality in non-smokers (HR = 1.29, 95% CI 1.04-1.61 in men and HR = 1.46, 95% CI 1.19-1.79 in women), whereas leanness was associated with mortality only among smoking men (HR = 1.39, 95% CI 1.09-1.77). CONCLUSION: Refinement of BMI categories using country of origin specific quintiles demonstrated significantly increased mortality in the upper quintile in both sexes, while according to the conventional values this association did not prevail in men. We propose the establishment of sex and origin-specific BMI categories when setting goals for disease prevention.

Visual outcome of mega-dose intravenous corticosteroid treatment in non-arteritic anterior ischemic optic neuropathy - retrospective analysis.

BACKGROUND: To date, non arteritic anterior ischemic optic neuropathy (NAION) is still incurable. We wish to evaluate the effect of intravenous (IV) corticosteroids on the visual outcome of NAION patients. METHODS: Visual parameters were retrospectively compared between NAION patients treated with IV corticosteroids and untreated NAION patients (control). Visual acuity (VA) and Humphrey automated static perimetry visual field (VF) defects of the affected eye were compared between groups at baseline, 1, 3, 6 months, and end of follow-up visits. The VF analysis consisted of number of quadrant involvements and mean deviation (MD). RESULTS: Each group comprised 23 patients (24 eyes). Mean initial VA was similar in the control and treatment groups (p = 0.8). VA at end of follow-up did not improve in either groups (p = 0.8 treated group, p = 0.1 control group). No improvement and no difference in VF defects were found by either quadrant analysis (p = 0.1 treated group, p = 0.5 control group) or MD analysis (p = 0.2, treated group, p = 0.9 control group). VA and VF parameters tended to be worse in the treated group, although without statistical significance. CONCLUSIONS: Our results suggest that IV corticosteroids may not improve the visual outcome of NAION patients. Since intravenous corticosteroids could potentially cause serious adverse effects, this treatment for NAION is questionable.

The association between frailty biomarkers and 20-year all-cause and cardiovascular mortality among community-dwelling older adults.

OBJECTIVES: While several biomarkers were previously associated with frailty and mortality, data are still contradicting. We aimed to evaluate the association between novel biomarkers and frailty among community-dwelling older adults to enhance understanding of the pathophysiology of frailty. METHODS: Nine hundred and sixty-three older adults were screened during the third phase (1999-2008) of the Israel study on Glucose Intolerance, Obesity, and Hypertension (GOH). Frailty was defined as sedentary individuals, past 10 years hospitalizations, or at least one of the following: body mass index (BMI) <21 kg/m2; albumin <3.2 g/dl; ≥2 major baseline diseases. Biomarkers were evaluated for their association with frailty, all-cause, and cardiovascular mortality. RESULTS: Mean baseline age was 72 ± 7 years, 471 (49%) were women, and 195 (20%) were classified as frail. Median follow-up for cardiovascular and all-cause mortality was 11 and 13 years, with 179 (18.6%) and 466 (48.4%) deaths recorded, respectively. Multivariable logistic regression showed greater odds for frailty with lower quartile of alanine aminotransferase (ALT) (OR = 1.8, 95%CI: 1.2-2.8, p = 0.01), and for each 5 µmol/L increment in homocysteine levels (OR = 1.3, 95%CI: 1.1-1.5, p = 0.001). Multivariate Cox regression showed greater all-cause and cardiovascular mortality risk for individuals with low ALT (HR = 1.6, 95%CI: 1.3-2.0, p < 0.001 and HR = 1.5, 95% CI: 1.0-2.2, p = 0.03, respectively), and high homocysteine (HR = 1.1, 95%CI: 1.1-1.3, p = 0.003 and HR = 1.2, 95%CI: 1.0-1.3, p = 0.04, respectively). Homocysteine association with mortality was more pronounced in those with baseline ischemic heart disease (IHD) compared with subjects free of IHD (P for interaction = 0.01). CONCLUSIONS: Lower ALT and higher homocysteine were associated with frailty, all-cause and cardiovascular mortality. These available and low-cost biomarkers underscore the nutritional and metabolic aspects of frailty when screening high-risk older adults, especially those with IHD, and may be considered as preferable screening biomarkers to be tested among these individuals for frailty and mortality risk.