Karen L. Falkner

Regular aspirin use and lung cancer risk.

BackgroundAlthough a large number of epidemiological studies have examined the role of aspirin in the chemoprevention of colon cancer and other solid tumors, there is a limited body of research focusing on the association between aspirin and lung cancer risk.MethodsWe conducted a hospital-based case-control study to evaluate the role of regular aspirin use in lung cancer etiology. Study participants included 868 cases with primary, incident lung cancer and 935 hospital controls with non-neoplastic conditions who completed a comprehensive epidemiological questionnaire. Participants were classified as regular aspirin users if they had taken the drug at least once a week for at least one year.ResultsResults indicated that lung cancer risk was significantly lower for aspirin users compared to non-users (adjusted OR = 0.57; 95% CI 0.41–0.78). Although there was no clear evidence of a dose-response relationship, we observed risk reductions associated with greater frequency of use. Similarly, prolonged duration of use and increasing tablet years (tablets per day × years of use) was associated with reduced lung cancer risk. Risk reductions were observed in both sexes, but significant dose response relationships were only seen among male participants. When the analyses were restricted to former and current smokers, participants with the lowest cigarette exposure tended to benefit most from the potential chemopreventive effect of aspirin. After stratification by histology, regular aspirin use was significantly associated with reduced risk of small cell lung cancer and non-small cell lung cancer.ConclusionsOverall, results from this hospital-based case-control study suggest that regular aspirin use may be associated with reduced risk of lung cancer.

Periodontal disease and risk of myocardial infarction: the role of gender and smoking

Background: Studies examining the association between periodontal disease and coronary heart disease have shown a consistent but weak to moderate relationship. Limited data have been reported in women and the role of smoking has not been fully clarified. Methods/Results: A population-based case–control study examining the association between periodontal disease (PD) and acute non-fatal myocardial infarction (MI) was conducted in Erie and Niagara counties in Western New York State. Cases (574) were discharged alive from local hospitals with MI diagnosis. Controls (887) were county residents randomly selected from the NY State Department of Motor Vehicles rolls and Health Care Financing Administration files. Periodontal disease was assessed using clinical attachment loss (CAL). Among men (415 cases), the odds ratio (OR) of the association between mean CAL (mm) and MI, adjusting for the effects of age, body mass index (BMI), physical activity, hypertension, cholesterol, diabetes, and total pack-years of cigarette smoking was 1.34 (1.15–1.57). In women (120 cases), the corresponding OR was 2.08 (1.47–2.94). The estimate of this association among non-smokers, also adjusting for age, gender, BMI, physical activity, hypertension, cholesterol, diabetes, and total pack-years of cigarette smoking, was 1.40 (1.06–1.86), while it was 1.49 (1.26–1.77) among smokers. Conclusions: This study provides evidence of an association between PD and incident MI in both genders. This association appears to be independent from the possible confounding effect of smoking.

Periodontal Disease and Recurrent Cardiovascular Events in Survivors of Myocardial Infarction (MI): The Western New York Acute MI Study

BACKGROUND Periodontal disease and cardiovascular disease (CVD) have been the focus of much research, but little is known about their roles in the recurrent event risk in patients with CVD. This study investigates whether periodontal disease is related to recurrent CVD events and mortality in survivors of incident myocardial infarction (MI). METHODS Participants (668 males and 216 females; mean age: 54 + or - 8.5 years) were recruited (1997 through 2004) from two western New York county hospitals and completed an interviewer-administered questionnaire regarding lifestyle habits, clinical measurements, and a comprehensive dental examination. The periodontal disease status was measured by the mean clinical attachment loss (AL). Follow-up surveys assessed hospitalizations or medical procedures; cardiovascular events were validated by medical records. A National Death Index (NDI) Plus search was conducted. The outcome was recurrent fatal and non-fatal cardiovascular events (International Classification of Diseases codes 390 to 450). RESULTS After an average follow-up of 2.9 years, 154 events were reported. Among never-smokers, the adjusted hazard ratio (95% confidence interval) for the mean clinical AL (millimeters) was 1.43 (1.09 to 1.89). No associations were found in ever-smokers (clinical AL by smoking interaction: P <0.05). CONCLUSION These findings indicate that periodontal disease may be an important factor in determining recurrent cardiovascular events in MI patients and not merely a marker for the effects of cigarette smoking.

Environmental exposure to polychlorinated biphenyls and breast cancer risk.

Breast cancer is a major public health problem in the United States and in most industrialized countries. Although epidemiologic studies have identified a number of established risk factors for this disease, these factors explain only a small proportion of breast cancer incidence. Environmental exposure has been implicated in breast cancer etiology because of the vast geographic variation in breast cancer incidence rates across countries and regions within countries. Further, the steady increase in breast cancer rates over the past decades points to a potential role of environmental exposure in its development. One suspected environmental factor is the polychlorinated biphenyls (PCBs), which were manufactured commercially for a variety of industrial applications from the 1930s until the 1970s. PCBs have been associated with estrogenic, tumor promoting, and immunosuppressive activities, all of which are relevant in the development of breast cancer. The purpose of this review is to summarize the growing body of epidemiological evidence on the association between environmental PCB exposure and breast cancer risk. Three major types of study design have been used to investigate such a relation: clinic-based case-control studies, retrospective case-control studies, and nested case-control studies. Although findings from clinic-based case-control studies tend to point to an adverse effect of high PCB body burden on risk, the results from the more methodologically sound retrospective and nested studies do not provide strong support for a role of PCBs in breast cancer development. The association between PCB exposure and risk among racially and genetically susceptible subgroups may warrant further investigation. Methodological challenges in the design and analysis of epidemiologic studies on PCBs and breast cancer risk are discussed.

Adapting the cognitive interview to enhance long-term (35 years) recall of physical activities.

The cognitive interview (CI) was modified for use in an epidemiological study in which respondents were asked to recall their daily physical activities from the distant past (35 years ago). In comparison to a traditional epidemiological interview, the CI elicited many more responses and also more precise responses. Several practical costs, however, were incurred by the CI: additional time to train interviewers and to conduct interviews and difficulties in coding the responses. The costs and benefits of conducting the CI are addressed, along with conceptual and methodological challenges. The article ends with an existential question: Is the CI a singular technique if it can be modified so radically for different settings?

Association between periodontal pathogens and risk of nonfatal myocardial infarction.

BACKGROUND The direct effect of periodontal pathogens on atherosclerotic plaque development has been suggested as a potential mechanism for the observed association between periodontal disease and coronary heart disease, but few studies have tested this theory. OBJECTIVES (i) To assess the association of periodontal pathogens in periodontal pockets with the risk of myocardial infarction (MI) and (ii) to assess whether an increase in the number of periodontal bacterial species increases the risk of MI. METHODS A total of 313 cases and 747 controls, consisting of Caucasian men and women from Western New York, aged 35 to 69 years, were recruited for this study. The presence of microorganisms was assessed by indirect immunofluorescence microscopy, using species-specific polyclonal and monoclonal serodiagnostic reagents. The presence of six periodontal pathogens, Porphyromonas gingivalis (Pg), Tannerella forsythensis (Tf), Prevotella intermedia (Pi), Campylobacter recta (Cr), Fusobacterium nucleatum (Fn), and Eubacterium saburreum (Es), and their co-occurrence (0-6) was compared with the odds of having myocardial infarction. RESULTS Univariate analyses revealed a higher percentage of the presence of each bacterium in cases compared to controls. In multivariate analyses, only Tf and Pi were statistically associated with an increase in the odds of having MI [Odds ratio OR=1.62; 95% CI (1.18-2.22); and 1.40; 95% (1.02-1.92), respectively] after adjusting for age, gender, education, cholesterol, high blood pressure, diabetes, and total pack-years of cigarette smoking. An increase in the number of different periodontal bacteria in pockets was also found to increase the odds of MI [adjusted OR=1.14; 95% CI (1.03-1.26)]. Participants who had three species or more of periodontal pathogens had about 2-fold increase in odds of having nonfatal MI than those who did not have any type of bacterial species [OR=2.01 (1.31-3.08)]. CONCLUSION The presence of periodontal pathogens, specifically Tf or Pi, and an increase in total burden of periodontal pathogenic species were both associated with increased odds of having MI. However, further studies are needed to better assess any causal relationship, as well as the biological mechanisms underlying this association.

Performance of Multiplex Cytokine Assays in Serum and Saliva among Community-Dwelling Postmenopausal Women

Multiplexing arrays increase the throughput and decrease sample requirements for studies employing multiple biomarkers. The goal of this project was to examine the performance of Multiplex arrays for measuring multiple protein biomarkers in saliva and serum. Specimens from the OsteoPerio ancillary study of the Women’s Health Initiative Observational Study were used. Participants required the presence of at least 6 teeth and were excluded based on active cancer and certain bone issues but were not selected on any specific condition. Quality control (QC) samples were created from pooled serum and saliva. Twenty protein markers were measured on five multiplexing array panels. Sample pretreatment conditions were optimized for each panel. Recovery, lower limit of quantification (LLOQ) and imprecision were determined for each analyte. Statistical adjustment at the plate level was used to reduce imprecision estimates and increase the number of usable observations. Sample pre-treatment improved recovery estimates for many analytes. The LLOQ for each analyte agreed with manufacturer specifications except for MMP-1 and MMP-2 which were significantly higher than reported. Following batch adjustment, 17 of 20 biomarkers in serum and 9 of 20 biomarkers in saliva demonstrated acceptable precision, defined as <20% coefficient of variation (<25% at LLOQ). The percentage of cohort samples having levels within the reportable range for each analyte varied from 10% to 100%. The ratio of levels in saliva to serum varied from 1∶100 to 28∶1. Correlations between saliva and serum were of moderate positive magnitude and significant for CRP, MMP-2, insulin, adiponectin, GM-CSF and IL-5. Multiplex arrays exhibit high levels of analytical imprecision, particularly at the batch level. Careful sample pre-treatment can enhance recovery and reduce imprecision. Following statistical adjustments to reduce batch effects, we identified biomarkers that are of acceptable quality in serum and to a lesser degree in saliva using Multiplex arrays.

A multilevel analysis of long-term psychological distress among Belarusians affected by the Chernobyl disaster

BACKGROUND Radiation contamination and sociopolitical instability following the Chernobyl nuclear power plant disaster have had a profound impact on Belarus. OBJECTIVE To investigate the factors that impact long-term mental health outcomes of this population almost 20 years after the disaster. STUDY DESIGN Cross-sectional study. METHODS In-person interviews were conducted with 381 men and women from two geographic areas of differing radiation contamination within Belarus. Participants completed surveys of demographics, psychosocial factors and psychological distress. Individual-level characteristics were combined with household-level measures of radiation contamination exposure and family characteristics to create multilevel predictive models of psychological distress. RESULTS Between-household effects accounted for 20% of variability in depression and anxiety scores, but only 8% of variability in somatization scores. Degree of chronic daily stressors showed a significant positive relationship with psychological distress, whereas mastery/controllability showed a significant inverse relationship with distress. At household level, perceived family problems, but not level of residential radiation contamination, was the best predictor of distress. CONCLUSIONS Multilevel modelling indicates that long-term psychological distress among Belarusians affected by the Chernobyl disaster is better predicted by stress-moderating psychosocial factors present in ones daily life than by level of residential radiation contamination.

Demographic and health factors associated with enrollment in posttrial studies: the Women's Health Initiative Hormone Therapy Trials.

Background After clinical trials end, continued follow-up of the assembled cohort often is desirable for additional research. Factors influencing participants’ decisions to consent to additional follow-up and how these shape posttrial cohorts have not been broadly studied. Purpose We examined how two re-enrollment campaigns and the passage of time altered features of the posttrial cohorts compared with the original Women’s Health Initiative (WHI) Hormone Therapy clinical trials. Methods We examined associations that markers of sociodemography, health, lifestyle, and on-trial experiences had with re-enrollment and contrasted the characteristics of successive posttrial cohorts with those of the original enrollees. Results The posttrial enrollment campaigns re-enrolled 81.1% and 82.5% of available women, respectively. Women who re-enrolled tended to have better health characteristics than those not re-enrolled. Compared to women of comparable age in the original cohort, women retained for the second posttrial follow-up less often had a history of cardiovascular disease (odds ratio (OR) = 0.36), hypertension (OR = 0.57), diabetes (OR = 0.59), or measured cognitive deficit (OR = 0.40). These women more often had graduated from high school (OR = 1.72) and had participated in other WHI trials (OR = 1.76). Limitations We have examined experience with creating follow-up cohorts from participants in a single study. Thus, our findings may not apply to other cohorts and protocols. Conclusions Posttrial enrollment in follow-up studies can be successful; however, the characteristics of the resulting cohort may differ substantially from the originally assembled group of trial participants. Collection during the original trial of potential predictors of differential re-enrollment may strengthen interpretation of findings.

Modelling changes in clinical attachment loss to classify periodontal disease progression

Abstract Aim The goal of this study was to identify progressing periodontal sites by applying linear mixed models (LMM) to longitudinal measurements of clinical attachment loss (CAL). Methods Ninety‐three periodontally healthy and 236 periodontitis subjects had their CAL measured bi‐monthly for 12 months. The proportions of sites demonstrating increases in CAL from baseline above specified thresholds were calculated for each visit. The proportions of sites reversing from the progressing state were also computed. LMM were fitted for each tooth site and the predicted CAL levels used to categorize sites regarding progression or regression. The threshold for progression was established based on the model‐estimated error in predictions. Results Over 12 months, 21.2%, 2.8% and 0.3% of sites progressed, according to thresholds of 1, 2 and 3 mm of CAL increase. However, on average, 42.0%, 64.4% and 77.7% of progressing sites for the different thresholds reversed in subsequent visits. Conversely, 97.1%, 76.9% and 23.1% of sites classified as progressing using LMM had observed CAL increases above 1, 2 and 3 mm after 12 months, whereas mean rates of reversal were 10.6%, 30.2% and 53.0% respectively. Conclusion LMM accounted for several sources of error in longitudinal CAL measurement, providing an improved method for classifying progressing sites.