Accounting for EGFR Mutations in Epidemiologic Analyses of Non-Small Cell Lung Cancers: Examples Based on the International Lung Cancer Consortium Data.

BACKGROUND: Somatic EGFR mutations define a subset of non-small cell lung cancers (NSCLC) that have clinical impact on NSCLC risk and outcome. However, EGFR-mutation-status is often missing in epidemiologic datasets. We developed and tested pragmatic approaches to account for EGFR-mutation-status based on variables commonly included in epidemiologic datasets and evaluated the clinical utility of these approaches. METHODS: Through analysis of the International Lung Cancer Consortium (ILCCO) epidemiologic datasets, we developed a regression model for EGFR-status; we then applied a clinical-restriction approach using the optimal cut-point, and a second epidemiologic, multiple imputation approach to ILCCO survival analyses that did and did not account for EGFR-status. RESULTS: Of 35,356 ILCCO patients with NSCLC, EGFR-mutation-status was available in 4,231 patients. A model regressing known EGFR-mutation-status on clinical and demographic variables achieved a concordance index of 0.75 (95% CI, 0.74-0.77) in the training and 0.77 (95% CI, 0.74-0.79) in the testing dataset. At an optimal cut-point of probability-score = 0.335, sensitivity = 69% and specificity = 72.5% for determining EGFR-wildtype status. In both restriction-based and imputation-based regression analyses of the individual roles of BMI on overall survival of patients with NSCLC, similar results were observed between overall and EGFR-mutation-negative cohort analyses of patients of all ancestries. However, our approach identified some differences: EGFR-mutated Asian patients did not incur a survival benefit from being obese, as observed in EGFR-wildtype Asian patients. CONCLUSIONS: We introduce a pragmatic method to evaluate the potential impact of EGFR-status on epidemiological analyses of NSCLC. IMPACT: The proposed method is generalizable in the common occurrence in which EGFR-status data are missing.

Loneliness as a gender-specific predictor of physical and mental health-related quality of life in older adults.

PURPOSE: Health-related quality of life (HRQOL) in older persons is influenced by physical and mental health, as well as by their social contacts and social support. Older women and men have disparate types of social networks; they each value social ties differently and experience loneliness in unique and personal ways. The aim of this study is, therefore, to determine the longitudinal association between loneliness and social isolation with HRQOL in older people-separated by gender. METHODS: Data stem from the third and fourth follow-up of the ESTHER study-a population-based cohort study of the older population in Germany. A sample of 2171 older women and men (mean age: 69.3 years, range 57-84 years) were included in this study; HRQOL was assessed by using the Short Form-12 questionnaire (SF-12). Data on physical and mental health, loneliness, and social networks were examined in the course of comprehensive home visits by trained study doctors. Gender-specific linear regression analyses were performed to predict physical quality of life (measured by the PCS, physical component score of the SF-12) and mental quality of life (measured by the MCS, mental component score) after three years, adjusted by socioeconomic variables as well as physical, mental, and social well-being. RESULTS: At baseline, PCS was 41.3 (SD: 10.0) in women and 42.2 (SD: 9.6) in men (p = .04). MCS was 47.0 (SD: 10.2) in women and 49.6 (SD: 8.6) in men (p < .001). In both genders, PCS and MCS were lower three years later. Loneliness at t0 was negatively associated with both PCS and MCS after three years (t1) among women, and with MCS but not PCS after three years among men. In both genders, the strongest predictor of PCS after three years was PCS at t0 (p < .001), while the strongest predictors of MCS after three years were MCS and PCS at t0. CONCLUSION: HRQOL in elderly women and men is predicted by different biopsychosocial factors. Loneliness predicts decreased MCS after three years in both genders, but decreased PCS after three years only in women. Thus, a greater impact of loneliness on the health of older women can be surmised and should therefore be considered in the context of their medical care.

Coping resources of heart failure patients - a comparison with cancer patients and individuals having no chronic condition results from the esther study.

BACKGROUND: Heart failure (HF) and cancer patients share similarities in symptom burden and depression prevalence. Coping resources, such as optimism have been associated with improved health-related quality of life (HRQoL) and mental health. OBJECTIVES: To investigate a wide range of resources in a large population-based sample of HF patients; to compare resources between three groups: HF patients, cancer patients, and individuals having no chronic condition. METHODS: This cross-sectional analysis was performed among n = 2761 subjects who participated in home visits during the 11-year follow-up of the epidemiological ESTHER study. Resources were assessed by trained medical doctors through a questionnaire that lists 26 items. One-way analyses of covariance (ANCOVAs) controlled for sociodemographic variables and depression were performed to compare resources between groups. RESULTS: Family and self-efficacy were the most frequently reported resources in all groups. HF patients reported optimism significantly less frequently as a resource in comparison to cancer patients (p=.031). HF patients showed significantly lower levels of resource factor 3 (positive attitude), compared to cancer patients (p=.006), and not chronically ill participants (p=.037). CONCLUSIONS: Family and self-efficacy seem to be the most important resources, regardless of diagnosis. HF patients appear to have significantly lower levels of resources concerning positive attitude, compared to cancer patients, and not chronically ill individuals. We suggest the development of psychosocial interventions to enhance optimism in HF.

Gender-specific predictors of generalized anxiety disorder symptoms in older adults: Results of a large population-based study.

BACKGROUND: Anxiety in older age is common. In comparison with men, older women experience higher levels of anxiety and show different patterns of co-occurring mental disorders. The aim of this study is to investigate gender-specific biopsychosocial predictors associated with GAD (Generalized Anxiety Disorder) symptoms after a period of three years in the elderly population. METHODS: Data were derived from the third (2008-2010) and the fourth follow-up (2011-2014) of the large population-based German ESTHER study. 2254 participants ages 55-85 were included in the study (52.3% female; 47.7% male). Generalized Anxiety Disorder Symptoms were measured using the GAD-7 questionnaire at both follow-ups. Linear regression analyses were performed to predict GAD severity after three years; the analyses were separated by gender and adjusted for demographic variables, biopsychosocial health, cognitive impairment, loneliness, and psychosocial resources. RESULTS: In women, GAD severity after three years (t1) was positively associated with younger age, depression symptoms, loneliness, and GAD severity at t0. In men, GAD severity was positively associated with somatic symptoms as well as with GAD severity at t0. In both genders GAD severity at baseline was the strongest predictor of elevated future anxiety symptoms. LIMITATIONS: GAD was examined by the use of questionnaires rather than by personal assessment; underreporting of GAD symptoms is therefore possible. CONCLUSIONS: Our study shows that an increase as well as a decrease of GAD severity in older women and men can be predicted by several biopsychosocial variables.

Evidence for underuse and overuse of antidepressants in older adults: Results of a large population-based study.

OBJECTIVES: Depression is common among elderly people. However, diagnosis and adequate treatment is frequently difficult. Research on underuse and overuse of antidepressants in elderly persons is scarce. This study investigates the utilization and appropriateness of pharmacological and psychological depression treatment in a large cohort of community-dwelling adults. METHODS: A subsample of 3117 participants (aged 55-85 y) of the third follow-up (2008-2010) of the large population-based German ESTHER study was included. Depression was assessed using the eight-item Patient Health Questionnaire (PHQ-8). In the course of a home visit, study doctors collected complete information on medication. Logistic regression analyses were conducted to determine the relationship of depression with both underuse and overuse of antidepressants. The analyses were then adjusted for socioeconomic variables, psychosomatic comorbidities, and motivation to seek help. RESULTS: One hundred sixty-three participants (5.2%; 95% confidence interval [CI], 4.5-6.1) fulfilled the criteria for major depression. Underuse of antidepressants was present in 126 depressed participants (77.3%; 70.1-83.5). Persons who were motivated to seek help, who had an established depression diagnosis, or who were taking more than five different medications had lower odds of underuse. Anxiety was associated with higher odds for underuse. Overuse of antidepressants (prescription without clinical indication) was found in 96 cases (41.7%; 35.3-48.4) of all antidepressant prescriptions. CONCLUSIONS: Depression treatment in older adults is frequently insufficient; it appears to depend on diagnosis as well as the patients' motivation to seek help. Education regarding the diagnosis of depression in the elderly as well as guidelines for appropriate treatment is needed.