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.

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.

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.

Childhood exposure to ionizing radiation to the head and risk of schizophrenia.

While the association between exposure to ionizing radiation and cancer is well established, its association with schizophrenia is unclear. The aim of our study was to assess risk of schizophrenia after childhood exposure to ionizing radiation to the head (mean dose: 1.5 Gy). The study population included an exposed group of 10,834 individuals irradiated during childhood for treatment of tinea capitis in the 1950s and two unexposed comparison groups of 5392 siblings and 10,834 subjects derived from the National Population Registry individually matched to the exposed group by age, sex (when possible), country of birth, and year of immigration to Israel. These groups were followed for a median 46 years for diagnosis of schizophrenia updated to December 2002. The Cox proportional hazards model stratified by matched sets was used to compare the risk of schizophrenia between the groups. Based on 1,217,531 person-years of follow-up, 451 cases were identified. No statistically significant association was found between radiation exposure and schizophrenia for the total group (hazard ratio per 1 Gy to the brain: 1.05, 95% confidence interval: 0.93-1.18) or within subgroups of sex, dose categories or latent period. When comparing a subgroup of subjects irradiated under 5 years of age with the matched unexposed group, the estimated hazard ratio reached 1.18 (95% confidence interval: 0.96-1.44; P = 0.1). The results of our analysis do not support an association between exposure to ionizing radiation and risk of schizophrenia. More research on possible effects of early exposure to ionizing radiation on schizophrenia specifically and brain tissue in general is needed.

Possible interaction between ionizing radiation, smoking, and gender in the causation of meningioma.

Data on the association between smoking and meningioma are inconsistent. The aim of this study was to assess the role of smoking in radiation- and non-radiation-related meningiomas. The study was designed as a 4-group case-control study, balanced for irradiation, including 160 irradiated meningioma case patients, 145 irradiated control subjects, 82 nonirradiated case patients, and 135 nonirradiated control subjects. The sources of these groups included a cohort of individuals who underwent radiotherapy (mean dose, 1.5 Gy to the brain) during childhood for treatment of tinea capitis, claims filed for radiation damage in the framework of a compensation law, and the Israel Cancer Registry. All tests of statistical significance were 2-sided. A statistically significantly elevated risk of meningioma was found among men who had ever smoked, compared with those who were never smokers (odds ratio [OR], 2.13; 95% confidence interval [CI], 1.09-4.15), increasing with smoking pack-years from 1.67 to 2.69 for <10 to >20 pack-years, respectively. Among women, an interaction between radiation and smoking was observed, expressed by a significant protective effect for meningioma (OR, 0.32; 95% CI, 0.14-0.77), with a strong dose-response association (P < .01) in non-irradiated women and a nonsignificant increased risk of meningioma among those who were irradiated (OR, 1.23; 95% CI, 0.68-2.23). Variation in the association between smoking and meningioma may be explained by effects of distinct host factors, such as past exposure to ionizing radiation and/or hormonal factors.

Serum uric acid for risk stratification of patients with coronary artery disease.

OBJECTIVES: In patients with coronary artery disease (CAD), elevated serum uric acid (SUA) levels may predict worse cardiovascular outcomes. It is known that SUA levels are influenced by renal function. We aimed to assess the predictive value of SUA while taking into account patients' renal function. METHODS: The primary end point (PEP) risk, including fatal or nonfatal myocardial infarction (MI) or sudden death, was assessed by SUA quintiles before and after adjustment for the estimated glomerular filtration rate (eGFR) in 2,796 nondiabetic CAD patients enrolled in the Bezafibrate Infarction Prevention study. RESULTS: The PEP risk increased from the lowest (11.8%) to highest SUA quintile (18.0%), p < 0.005, respectively. After adjustment for age, sex, smoking, prior MI, metabolic syndrome variables, NYHA classes II-IV, heart rate and treatment with bezafibrate, diuretics, angiotensin-converting enzyme inhibitors, beta-blockers, calcium channel blockers and antiplatelets, the highest SUA quintile exhibited the highest PEP risk [hazard ratio (HR): 1.47 (95% CI: 1.06-2.04)]. Patients in the highest - compared with those in the lowest - quintiles continued to demonstrate an increased PEP risk [HR: 1.46 (95% CI: 1.04-2.06)], even after additional adjustment for the eGFR. CONCLUSION: In nondiabetic patients with CAD, elevated SUA levels are associated with an increased risk of cardiac events, independent of renal function.

Smoking and risk of glioma: a meta-analysis.

OBJECTIVE: Although causal relationships between smoking and cancer risk have been established for many sites, most studies of brain cancer have not supported an association. However, two recent cohort studies showed increased risks of glioma among smokers. We quantified the association between smoking and glioma through a meta-analysis of the literature. METHODS: Of 20 eligible studies, 17 (6 cohort and 11 case­control) were included in an analysis of ever versus never smoking. Multivariate-adjusted risk estimates in the papers were pooled to calculate cumulative risk. RESULTS: The cumulative estimated risk associated with ever smoking was 1.06 (95% CI: 0.97­1.15), for all, 1.10 (95% CI: 1.01­1.20) for cohort, and 1.00 (95% CI: 0.88­1.15) for case­control studies. A significantly increased risk associated with past smoking was noted for cohort studies, OR = 1.16 (p = 0.007), while an increased risk of borderline significance was seen for all studies, OR = 1.10 (p = 0.08). In general, dose­response analysis did not support an association and was limited because very few studies included these variables and could be pooled. CONCLUSION: Overall, results of pooling of all studies suggested that smoking is not associated with risk of glioma. However, the small but significant increased risk seen for cohort studies remains to be clarified.

Smoking and risk of parotid gland tumors: a nationwide case-control study.

BACKGROUND: Because existing data regarding the relation between smoking and salivary gland tumors are sparse, tobacco is currently not classified as a salivary gland carcinogen. The objective of the current study was to assess the association between smoking and benign and malignant parotid gland tumors (PGTs) in a nationwide study. METHODS: The sample included 459 patients with incident PGT, aged > or =18 years, who were diagnosed between 2001 and 2003 and a group of 1265 individually matched, population-based controls. Analyses of the risk of PGT associated with various smoking variables were performed by using conditional logistic regression. Data also were stratified by histologic type; statistical significance tests were 2-sided. RESULTS: Ever smoking cigarettes was associated with an odds ratio (OR) of 1.66 (95% confidence interval [95% CI], 1.31-2.11) for developing a PGT. The risk was strongest for early ages at smoking initiation, and trends of increasing risk were observed with increasing smoking intensity, pack-years, latent period, and smoking duration (P for trend <.001 for each). Analysis by histologic type indicated remarkably high risks for Warthin tumor (OR for ever cigarette smokers: 15.3; 95% CI, 6.1-38.5). For pleomorphic adenomas and malignant tumors, the risks associated with ever smoking were 1.01 (95% CI, 0.75-1.37) and 1.69 (95% CI, 0.81-3.51), respectively. CONCLUSIONS: Smoking plays an important role in the development of Warthin tumor. Although no association was observed for pleomorphic adenoma, the possible indication of increased risk of malignant tumors requires further investigation in larger studies.

Acute myocardial infarction preceded by potential triggering activities: angiographic and clinical characteristics.

BACKGROUND: In an investigation of the relationship between myocardial infarction (MI) preceded by certain activities or events and coronary angiographic data, including the extent of atherothrombotic involvement during acute MI, we hypothesized that when comparing patients with MI that was preceded by potential triggering activities (PTA "+") to MI without PTA, the former might have a distinct pathogenic basis exhibiting different angiographic and clinical features. METHODS: In the framework of a national survey on acute coronary syndromes conducted during a 2-month period in 2002, 662 acute MI patients with complete angiographic data were divided into two groups, according to whether or not they reported the presence of specific unusual events or activities immediately preceding the onset of MI. RESULTS: One hundred and one patients with PTA "+" MI were younger, and included a higher proportion of smokers than their counterparts (n=561), who were characterized by a higher frequency of hypertension and diabetes. After adjustment for age, gender, prior MI or CABG, diabetes, hypertension, current smoking, serum creatinine level, left ventricular ejection fraction less than 30%, re-ischemia and Killip class II+, 30-day, 6 month and 1-year mortality was similar between the two groups. The incidence of LAD disease (P<0.01), 3-vessel coronary disease (P<0.03) and TIMI flow 0 or 1 after coronary angioplasty was significantly lower (P<0.02) in patients with PTA "+" MI, while infarct-related right coronary artery (RCA) obstruction was significantly higher (OR: 1.7; 95% CI: 1.0-2.9). CONCLUSION: Further investigation is needed in order to confirm the association between angiographic data and potential triggering activities observed in our study, and to determine the mechanisms responsible for this finding.

Is hypoglycaemia a marker for increased long-term mortality risk in patients with coronary artery disease? An 8-year follow-up.

BACKGROUND: No information is available regarding the association between low plasma glucose levels and cause-specific and all-cause mortality in patients with coronary artery disease (CAD). We aimed to investigate the relationship between hypoglycaemia and all-cause, cardiovascular and cancer mortality in a large population of patients with CAD. DESIGN: Patients were recruited from the BIP (Bezafibrate Infarction Prevention) registry, a secondary prevention prospective multicentre randomized, placebo-controlled, double-blind trial aimed to assess the efficacy of bezafibrate in reduction of coronary events. METHODS: The study included 14,670 CAD patients aged 45-74, divided into six groups: (1) hypoglycaemic (up to 69 mg/dl); (2) low normal (70-79 mg/dl); (3) euglycaemic (80-109 mg/dl); (4) impaired fasting glucose (IFG) (110-125 mg/dl); (5) borderline diabetics (126-139 mg/dl); (6) diabetics (> or 140 mg/dl). RESULTS: Patients comprised 131 with hypoglycaemia (0.9%), 731 with low normal glucose (5%), 9308 euglycaemic (63.4%), 1577 with IFG (10.7%), 617 borderline diabetics (4.2%) and 2306 diabetics (15.7%). Over a mean 8-year follow-up, crude all-cause mortality was higher in both diabetic (31.8%) and hypoglycaemic groups (25.2%) as compared with euglycaemics (14.9%; P<0.0001); CAD mortality was higher in diabetic and borderline groups (17.8 and 13.3%, respectively, versus 7.9% in euglycaemics; P<0.0001). The highest prevalence of cancer mortality was documented in the hypoglycaemic group (6.1 versus 2.9% in euglycaemics; P<0.02). Actuarial survival curves showed the lowest mortality in euglycaemic and low normal groups; the highest was seen in diabetic and hypoglycaemic patients. Intermediate values were found in borderline and IFG patients. After adjustment for variables, a significantly higher mortality rate was seen in hypoglycaemics when compared with euglycaemics (P<0.0001). Hypoglycaemia was identified as a predictor of increased all-cause and cancer mortality with a hazard ratio (HR) of 1.84 [95% confidence interval (CI) 1.29-2.61] and 2.26 (95% CI 1.12-4.57), respectively, but not of increased CAD mortality, with HR 1.30 (95% CI 0.73-2.29). CONCLUSIONS: Over a mean 8-year follow-up, hypoglycaemia emerges as a marker for substantially increased all-cause and cancer mortality among patients with CAD presenting with low fasting glucose levels.

Functional class in patients with heart failure is associated with the development of diabetes.

PURPOSE: Recent reports suggest that decreased functional capacity in patients with heart failure may be associated with abnormalities in glucose metabolism. We followed patients with coronary artery disease who participated in the Bezafibrate Infarction Prevention study to determine the incidence of diabetes by baseline functional status during a 7.7-year follow-up. METHODS: The sample comprised 2616 nondiabetic patients aged 45 to 74 years with a fasting blood glucose level <7 mmol/L (126 mg/dL). They were divided into three groups by New York Heart Association (NYHA) criteria: class I (n = 1986 patients), class II (n = 518), and class III (n = 112). The detection of a fasting blood glucose level > or =7 mmol/L during follow-up was defined as the criterion for the development of diabetes. RESULTS: The study groups had similar demographic and clinical characteristics, except that patients with symptomatic heart failure (NYHA class II or III) were more likely to have angina. During follow-up, diabetes developed in 259 patients (13%) in NYHA class I, 76 (15%) in class II, and 22 (20%) in class III (P for trend = 0.05). At the last visit, patients in NYHA class III were twice as likely (17% [n = 19]) to have fasting blood glucose levels > or =7 mmol/L as those in NYHA class I (7.8% [n = 154]) or class II (8.7% [n = 45]) (P = 0.005). In a multivariate analysis, NYHA class III was associated with a 1.7-fold (95% confidence interval [CI]: 1.1 to 2.6) increase in the rate of development of diabetes, but NYHA class II was not (hazard ratio = 1.0; 95% CI: 0.8 to 1.3). CONCLUSION: Among patients with coronary artery disease, advanced heart failure (NYHA class III) is associated with a significantly increased risk of developing diabetes during a 6- to 9-year follow-up.

Is immigration associated with an increase in risk factors and mortality among coronary artery disease patients? A cohort study of 13,742 patients.

BACKGROUND: Clinical studies showing an association between immigration and increased prevalence of coronary risk factors or mortality rate in patients with coronary artery disease are scarce. OBJECTIVES: To compare the risk profile and mortality of coronary patients born in Israel with those who immigrated to Israel, and to determine whether recent immigration is associated with greater risk among immigrants from the Soviet Union. METHODS: Demographic, clinical, and laboratory data were collected on chronic coronary artery disease patients from 18 Israeli medical centers during the screening period of the Bezafibrate Infarction Prevention Study in the early 1990s. Data on mortality after a mean 7.7 year follow-up were obtained from the Israel Population Registry. RESULTS: While significant differences in mortality (14.7% vs. 18.5%, P < 0.001) were observed between Israeli-born patients and immigrants respectively, the mortality in these groups was similar when compared within specific age groups. Immigrants suffered more from hypertension and angina pectoris, and their New York Heart Association functional limitation class was higher, as compared to their Israeli-born counterparts. A multivariate analysis of mortality comparing patients from the Soviet Union who immigrated after 1970 with those who immigrated before 1970 showed an increased risk for newer immigrants, with a hazard ratio of 1.69 (95% confidence interval 1.19-2.40) for those immigrating between 1970 and 1984, and 1.68 (95% CI 1.01-2.28) for those immigrating between 1985 and 1991. CONCLUSION: The worse profile and prognosis observed among patients who recently emigrated from the Soviet Union cannot be explained by traditional risk factors for CAD such as smoking, diabetes, hypertension, and lipid disorders. Further investigation, including variables such as psychological stress to which immigrants are more exposed than others, is needed.

Severity of angina pectoris and risk of ischemic stroke.

BACKGROUND AND PURPOSE: Ischemic stroke and coronary heart disease (CHD) share risk factors and pathogenic process, ie, atherosclerosis and thrombosis. We examined the relationship between severity of angina pectoris and its accompanying characteristics and the risk of incident ischemic stroke. METHODS: We traced 3122 patients with stable CHD, included in a secondary prevention trial of lipid modification, the Bezafibrate Infarction Prevention trial. CHD was documented by a history of myocardial infarction > or =6 months and < 5 years before enrollment and/or stable angina pectoris with evidence of ischemia confirmed by ancillary diagnostic testing. Severity of angina pectoris was assessed according to the Canadian Cardiovascular Society angina classification, and heart failure functional class according to the New York Heart Association (NYHA) classification. Patients with severe heart failure or unstable angina on enrollment were excluded. RESULTS: During a mean follow-up period of 8.2 years, 186 patients developed an ischemic stroke. The cumulative rate of ischemic stroke increased in a dose-response manner from 4.7% in patients with no angina to 5.7%, 8.4%, and 12.9% in patients with angina classes 1, 2, and 3, respectively (P<0.001). Patients with NYHA functional class 1 had a 5.5% rate of ischemic stroke versus 7.3% and 9.6% in patients with classes 2 and 3, respectively (P=0.05). In a Cox proportional-hazard model adjusting for conventional risk factors and potential confounders, the hazard ratio associated with angina class 1 was 1.20 (95% CI, 0.83 to 1.74); class 2, 1.66 (95% CI, 1.12 to 2.45); and class 3, 2.35 (95% CI, 1.08 to 5.13), as compared with patients with no angina. Hazard ratios of ischemic stroke associated with conventional risk factors were 1.55 for a 10-year age increment, 2.16 for diabetes mellitus, 1.81 for current smoking, and 1.29 for a 20 mm Hg increase in systolic blood pressure. CONCLUSIONS: Severity of angina pectoris in patients with stable CHD predicts an increased risk of subsequent ischemic stroke. The association between angina class and incident ischemic stroke is independent of traditional vascular risk factors.