Differential and Joint Effects of Metformin and Statins on Overall Survival of Elderly Patients with Pancreatic Adenocarcinoma: A Large Population-Based Study.

Background: Published evidence indicates that individual use of metformin and statin is associated with reduced cancer mortality. However, their differential and joint effects on pancreatic cancer survival are inconclusive.Methods: We identified a large population-based cohort of 12,572 patients ages 65 years or older with primary pancreatic ductal adenocarcinoma (PDAC) diagnosed between 2008 and 2011 from the Surveillance, Epidemiology, and End Results (SEER)-Medicare-linked database. Exposure to metformin and statins was ascertained from Medicare Prescription Drug Event files. Cox proportional hazards models with time-varying covariates adjusted for propensity scores were used to assess the association while controlling for potential confounders.Results: Of 12,572 PDAC patients, 950 (7.56%) had used metformin alone, 4,506 (35.84%) had used statin alone, and 2,445 (19.45%) were dual users. Statin use was significantly associated with improved overall survival [HR, 0.94; 95% confidence interval (CI), 0.90-0.98], and survival was more pronounced in postdiagnosis statin users (HR, 0.69; 95% CI, 0.56-0.86). Metformin use was not significantly associated with overall survival (HR, 1.01; 95% CI, 0.94-1.09). No beneficial effect was observed for dual users (HR, 1.00; 95% CI, 0.95-1.05).Conclusions: Our findings suggest potential benefits of statins on improving survival among elderly PDAC patients; further prospective studies are warranted to corroborate the putative benefit of statin therapy in pancreatic cancer.Impact: Although more studies are needed to confirm our findings, our data add to the body of evidence on potential anticancer effects of statins. Cancer Epidemiol Biomarkers Prev; 26(8); 1225-32. ©2017 AACR

A parsimonious explanation for intersecting perinatal mortality curves: understanding the effects of race and of maternal smoking

BACKGROUND: Neonatal mortality rates among black infants are lower than neonatal mortality rates among white infants at birth weights <3000 g, whereas white infants have a survival advantage at higher birth weights. This finding is also observed when birth weight-specific neonatal mortality rates are compared between infants of smokers and non-smokers. We provide a parsimonious explanation for this paradoxical phenomenon. METHODS: We used data on births in the United States in 1997 after excluding those with a birth weight <500 g or a gestational age <22 weeks. Birth weight- and gestational age-specific perinatal mortality rates were calculated per convention (using total live births at each birth weight/gestational age as the denominator) and also using the fetuses at risk of death at each gestational age. RESULTS: Perinatal mortality rates (calculated per convention) were lower among blacks than whites at lower birth weights and at preterm gestational ages, while blacks had higher mortality rates at higher birth weights and later gestational ages. With the fetuses-at-risk approach, mortality curves did not intersect; blacks had higher mortality rates at all gestational ages. Increases in birth rates and (especially) growth-restriction rates presaged gestational age-dependent increases in perinatal mortality. Similar findings were obtained in comparisons of smokers versus nonsmokers. CONCLUSIONS: Formulating perinatal risk based on the fetuses-at-risk approach solves the intersecting perinatal mortality curves paradox; blacks have higher perinatal mortality rates than whites and smokers have higher perinatal mortality rates than nonsmokers at all gestational ages and birth weights

Associations of Hair Dye and Relaxer Use with Breast Tumor Clinicopathologic Features: Findings from the Women’s Circle of Health Study

Background Building upon our earlier findings of significant associations between hair dye and relaxer use with increased breast cancer risk, we evaluated associations of select characteristics of use with breast tumor clinicopathology. Methods Using multivariable-adjusted models we examined the associations of interest in a case-only study of 2998 women with breast cancer, overall and stratified by race and estrogen receptor (ER) status, addressing multiple comparisons using Bonferroni correction. Results Compared to salon application of permanent hair dye, home kit and combination application (both salon and home kit application) were associated with increased odds of poorly differentiated tumors in the overall sample. This association was consistent among Black (home kit: OR 2.22, 95 % CI: 1.21–5.00; combination: OR 2.46, 95 % CI: 1.21–5.00), but not White women, and among ER+ (home kit: OR 1.47, 95 % CI: 0.82–2.63; combination: OR 2.98, 95 % CI: 1.62–5.49) but not ER-cases. Combination application of relaxers was associated with increased odds of tumors \u3e2.0 cm vs. \u3c1.0 cm (OR = 1.82, 95 % CI: 1.23–2.69). Longer duration and earlier use of relaxers and combination application of permanent hair dyes and relaxers were associated with breast tumor features including higher tumor grade and larger tumor size, which often denote more aggressive phenotypes, although the findings did not maintain significance with Bonferroni correction. Conclusions These novel data support reported associations between hair dye and relaxer use with breast cancer, showing for the first time, associations with breast tumor clinicopathologic features. Improved hair product exposure measurement is essential for fully understanding the impact of these environmental exposure with breast cancer and to guide risk reduction strategies in the future

Pathways between objective and perceived neighborhood factors among Black breast cancer survivors

Background Mounting evidence supports associations between objective neighborhood disorder, perceived neighborhood disorder, and health, yet alternative explanations involving socioeconomic and neighborhood social cohesion have been understudied. We tested pathways between objective and perceived neighborhood disorder, perceived neighborhood social cohesion, and socioeconomic factors within a longitudinal cohort. Methods Demographic and socioeconomic information before diagnosis was obtained at interviews conducted approximately 10 months post-diagnosis from participants in the Women’s Circle of Health Follow-up Study – a cohort of breast cancer survivors self-identifying as African American or Black women (n = 310). Neighborhood perceptions were obtained during follow-up interviews conducted approximately 24 months after diagnosis. Objective neighborhood disorder was from 9 items audited across 23,276 locations using Google Street View and scored to estimate disorder values at each participant’s residential address at diagnosis. Census tract socioeconomic and demographic composition covariates were from the 2010 U.S. Census and American Community Survey. Pathways to perceived neighborhood disorder were built using structural equation modelling. Model fit was assessed from the comparative fit index and root mean square error approximation and associations were reported as standardized coefficients and 95% confidence intervals. Results Higher perceived neighborhood disorder was associated with higher objective neighborhood disorder (β = 0.20, 95% CI: 0.06, 0.33), lower neighborhood social cohesion, and lower individual-level socioeconomic factors (final model root mean square error approximation 0.043 (90% CI: 0.013, 0.068)). Perceived neighborhood social cohesion was associated with individual-level socioeconomic factors and objective neighborhood disorder (β = − 0.11, 95% CI: − 0.24, 0.02). Conclusion Objective neighborhood disorder might be related to perceived disorder directly and indirectly through perceptions of neighborhood social cohesion

Conducting Molecular Epidemiological Research in the Age of HIPAA: A Multi-Institutional Case-Control Study of Breast Cancer in African-American and European-American Women

Breast cancer in African-American (AA) women occurs at an earlier age than in European-American (EA) women and is more likely to have aggressive features associated with poorer prognosis, such as high-grade and negative estrogen receptor (ER) status. The mechanisms underlying these differences are unknown. To address this, we conducted a case-control study to evaluate risk factors for high-grade ER- disease in both AA and EA women. With the onset of the Health Insurance Portability and Accountability Act of 1996, creative measures were needed to adapt case ascertainment and contact procedures to this new environment of patient privacy. In this paper, we report on our approach to establishing a multicenter study of breast cancer in New York and New Jersey, provide preliminary distributions of demographic and pathologic characteristics among case and control participants by race, and contrast participation rates by approaches to case ascertainment, with discussion of strengths and weaknesses

Individual and joint effects of metformin and statins on mortality among patients with high-risk prostate cancer.

BACKGROUND: Pre-clinical studies suggest that metformin and statins may delay prostate cancer (PCa) metastases; however, data in humans are limited. To the best of our knowledge, this is the first human study aimed to quantify the individual and joint effects of statin and metformin use among patients with high-risk PCa. METHODS: This population-based retrospective cohort study identified patients from the Surveillance, Epidemiology, and End Results (SEER)-Medicare linked database. Exposure to metformin and statins was ascertained from Medicare Prescription Drug Event files. The association with all-cause and PCa mortality were evaluated using Cox proportional hazard model with competing causes of death, where propensity scores were used to adjusted imbalances in covariates across groups. RESULTS: Based on 12 700 patients with high-risk PCa, statin alone or in combination with metformin was significantly associated with reduced all-cause mortality (Hazard Ratio [HR]: 0.89; 95% Confidence Interval [CI]: 0.83, 0.96; and HR: 0.75; 95% CI, 0.67-0.83, respectively) and PCa mortality (HR, 0.80; 95% CI: 0.69, 0.92) and 0.64; 95% CI, d 0.51-0.81, respectively. The effects were more pronounced in post-diagnostic users: combination use of metformin/statins was associated with a 32% reduction in all-cause mortality (95% CI, 0.57-0.80), and 54% reduction in PCa mortality (95% CI, 0.30-0.69). No significant association of metformin alone was observed with either all-cause mortality or PCa mortality. CONCLUSIONS: Statin use alone or in combination with metformin was associated with lower all-cause and PCa mortality among high-risk patients, particularly in post-diagnostic settings; further studies are warranted

A parsimonious explanation for intersecting perinatal mortality curves: understanding the effect of plurality and of parity

BACKGROUND: Birth weight- and gestational age-specific perinatal mortality curves intersect when compared across categories of maternal smoking, plurality, race and other factors. No simple explanation exists for this paradoxical observation. METHODS: We used data on all live births, stillbirths and infant deaths in Canada (1991–1997) to compare perinatal mortality rates among singleton and twin births, and among singleton births to nulliparous and parous women. Birth weight- and gestational age-specific perinatal mortality rates were first calculated by dividing the number of perinatal deaths at any given birth weight or gestational age by the number of total births at that birth weight or gestational age (conventional calculation). Gestational age-specific perinatal mortality rates were also calculated using the number of fetuses at risk of perinatal death at any given gestational age. RESULTS: Conventional perinatal mortality rates among twin births were lower than those among singletons at lower birth weights and earlier gestation ages, while the reverse was true at higher birth weights and later gestational ages. When perinatal mortality rates were based on fetuses at risk, however, twin births had consistently higher mortality rates than singletons at all gestational ages. A similar pattern emerged in contrasts of gestational age-specific perinatal mortality among singleton births to nulliparous and parous women. Increases in gestational age-specific rates of growth-restriction with advancing gestational age presaged rising rates of gestational age-specific perinatal mortality in both contrasts. CONCLUSIONS: The proper conceptualization of perinatal risk eliminates the mortality crossover paradox and provides new insights into perinatal health issues

Social-class gradient in childhood asthma : the nature of the link and issues of measurement

The objectives of this thesis were: (i) to examine the relationship and the nature of the link of socioeconomic status (SES) to an objective indicator of childhood asthma; (ii) to quantify the agreement between area-based SES measures and SES assessed at the level of the individual; and (iii) to compare the test characteristics of asthma as evidenced by questionnaire, exercise and methacholine challenges without assuming a gold standard. We carried out a cross-sectional study of 989 Montreal elementary school children in an area where there is universal access to medical care through state-funded health insurance. A questionnaire was completed by parents, and the children performed spirometry before and after a free-running exercise challenge. Street address information and parental occupation were used to establish neighborhood and individual-level SES indicators respectively. A sub-sample of 332 children underwent allergy skin and methacholine bronchoprovocation tests, and indoor home measurements of NO$sb2$, PM$sb{10}$, dust-mites and various types of moulds were performed.Low SES was associated with an increased likelihood of exercise-induced bronchospasm (EIB), lower FEV$sb1$ and FVC, but not with FEV$sb1$/FVC, a measure of airway calibre. With lower SES the likelihood of positive allergy skin tests decreased for cat, trees and grasses but increased for cockroach and moulds.Of the host factors examined, birthweight was positively associated with FVC and FEV$sb1$ while airway responsiveness to methacholine increased as birthweight decreased. Pre-term birth independent of birthweight was associated with a lower FEV$sb1$/FVC. Of the environmental factors, increasing exposure to household tobacco smoke and smoking during pregnancy were found to be associated with larger FVC and lower FEV$sb1$/FVC. The current presence of a cat and lower respiratory infection prior to the age of 2 years (LRI) were associated with EIB. Increasing usual dietary salt intake was also found to be associated with higher methacholine responsiveness. Part of the observed relationship between SES and indicators of asthma was mediated by the indoor environmental pollutants.There was poor agreement between the area-based and the individual-level SES measures even when used to classify children into broad SES categories. Using a Bayesian approach, comparison of the three tests for measuring asthma revealed exercise challenge to perform least well compared to a questionnaire or methacholine provocation in terms of the test characteristics when the purpose was to chose a single test for identifying asthma in community based studies.The results provide evidence suggesting that SES is an important risk factor for childhood asthma. This further suggests that excess morbidity and mortality from asthma in inner city areas of large American cities is not only due to differential access to health care but that under-utilization of health care as well as host, dietary and environmental factors associated with social disadvantage are also important

Birthweight and Preterm Birth in Relation to Indicators of Childhood Asthma

BACKGROUND: Early life events may have long term consequences on respiratory health including the risk of developing asthma