Financial strain across 25 years and women's bladder health: a life course perspective.

BACKGROUND: A small number of cross-sectional studies have found that financial insecurity-a social determinant of health-is associated with lower urinary tract symptoms. OBJECTIVE: This study aimed to examine (1) whether women in the Coronary Artery Risk Development in Young Adult Study with higher levels of financial strain, assessed at 7 time points across 25 years beginning in 1985-1986, were more likely to report lower urinary tract symptoms and impact after the 2010-2011 financial strain assessment and (2) whether healthcare access and comorbidities mediated potential associations. STUDY DESIGN: This prospective cohort study recruited Black and White participants aged 18 to 30 years at baseline (1985-1986) from the populations of 4 US cities. The analytical sample was composed of women with complete data for analyses involving financial strain trajectories across 7 assessments (n=841) and mediation tests of data collected at 4 assessments (n=886). The outcome variable was previously developed through a cluster analysis of urinary incontinence severity, urinary incontinence impact, other lower urinary tract symptoms severity, and their impact in 2012-2013, which yielded 4 lower urinary tract symptoms and impact cluster categories: women with no symptom or very mild symptoms and no impact vs women with mild, moderate, or severe symptoms and impact. Financial strain was defined as finding it "very hard," "hard," or "somewhat hard" (vs "not very hard") to pay for the very basics, such as food, heating, and medical care. Using proportional odds logistic regression, cluster categories were regressed on the financial strain trajectory group, adjusting for age, race, education, and parity. For mediation analyses, separate financial strain variables (difficulty paying for the very basics, such as food and heating, and difficulty paying for medical care) were created by combining 1995-1996 and 2000-2001 values. Two healthcare access variables (difficulty receiving care and underutilization of care) and a single comorbidity index (smoking, physical inactivity, body mass index, hypertension, diabetes mellitus, and depressive symptoms) were created by combining 2005-2006 and 2010-2011 values. Regression analyses and structural equation modeling were used to test whether healthcare access and comorbidities mediated associations between financial strain and lower urinary tract symptoms and impact cluster categories. RESULTS: In comparison to women who were consistently not financially strained, women who were consistently strained (odds ratio, 2.10; 95% confidence interval, 1.13-3.91), shifted into being strained (odds ratio, 2.00; 95% confidence interval, 1.29-3.10), or experienced >1 shift in strain (odds ratio, 1.99; 95% confidence interval, 1.46-2.71) had roughly twice the odds of reporting greater lower urinary tract symptoms and impact. Underutilization of healthcare and comorbidities mediated the association between difficulty paying for medical care and lower urinary tract symptoms and impact. In the structural equation model, difficulty paying for medical care and underutilization of care were associated (ß=.31; P<.01), as was underutilization of care and greater lower urinary tract symptoms and impact (ß=.09; P<.01). Moreover, difficulty paying for medical care and the comorbidity index were associated (ß=.34; P<.01), as was the comorbidity index and greater lower urinary tract symptoms and impact (ß=.24; P<.01). Collectively, these mediation pathways eliminated a direct association between difficulty paying for medical care and lower urinary tract symptoms and impact. CONCLUSION: Underutilization of healthcare and comorbidities explained an association between financial strain (difficulty paying for medical care) and lower urinary tract symptoms and impact. Research is needed to confirm the findings and examine other mechanisms that may further explain the association. Accumulated evidence may inform future policies and practices.

Job strain, occupation, and bladder health among women.

OBJECTIVES: Lower urinary tract symptoms (LUTS) are common among employed women. An underexplored topic is whether characteristics of women's occupations may influence LUTS. The present study examined whether job strain and its individual components (psychological demands, decision latitude) were associated with greater LUTS and their impact and whether, compared to managerial and professional occupations, occupations characterized by manual labor, sales, service, nursing, and teaching were associated with greater LUTS and their impact. METHODS: Coronary Artery Risk Development in Young Adults cohort study data were analyzed. Job strain and occupation were assessed in 1987-88 and 1995-96. In 2012-13, LUTS and their impact were assessed. LUTS/impact category (a composite variable ranging from bladder health to mild, moderate, and severe LUTS/impact) was regressed on job strain and occupation in separate analyses, adjusting for age, race, parity, education, and financial hardship (n = 1006). RESULTS: Job strain and its individual components were not associated with LUTS/impact. In comparison to managerial and professional occupations, service occupations in 1987-88 and 1995-96 were both associated with greater odds of LUTS/impact in proportional odds logistic regression analyses. Employment as a nurse, health assistant, or health aide in 1995-96 was associated with greater odds of any LUTS/impact versus bladder health. Support positions in 1987-88 and sales positions in 1995-96 were associated with greater odds of moderate or severe LUTS/impact versus bladder health or mild LUTS/impact. CONCLUSIONS: Future research should examine characteristics of workplaces that may promote or constrain bladder health (e.g., time and autonomy to void when desired, infrastructure to void).

Adverse Childhood Experiences and Lower Urinary Tract Symptoms and Impact Among Women.

PURPOSE: This study utilizes CARDIA (Coronary Artery Risk Development in Young Adults) cohort study data to examine whether (1) family-based adverse childhood experiences, recalled by women aged 32 to 47, are associated with lower urinary tract symptoms and their impact, a composite variable with 4 levels (bladder health and mild, moderate, or severe lower urinary tract symptoms/impact), and (2) extensiveness of women's social networks in adulthood attenuates an association between adverse childhood experiences and lower urinary tract symptoms/impact. MATERIALS AND METHODS: In 2000-2001, frequency of adverse childhood experiences exposure was retrospectively assessed. In 2000-2001, 2005-2006, and 2010-2011, extensiveness of social networks was assessed; scores were averaged. In 2012-2013, lower urinary tract symptoms/impact data were collected. Logistic regression analyses examined whether adverse childhood experiences, extensiveness of social networks, and their interaction were associated with lower urinary tract symptoms/impact, adjusting for age, race, education, and parity (n=1,302). RESULTS: Recall of more frequent family-based adverse childhood experiences was associated with report of more lower urinary tract symptoms/impact over 10 years later (OR=1.26, 95% CI=1.07, 1.48). Social networks during adulthood appeared to attenuate the association between adverse childhood experiences and lower urinary tract symptoms/impact (OR=0.64, 95% CI=0.41, 1.02). Among women with less extensive social networks, estimated probability of experiencing moderate or severe lower urinary tract symptoms/impact vs bladder health or mild lower urinary tract symptoms/impact was 0.29 and 0.21 for those reporting an adverse childhood experiences frequency corresponding to more than "a little" vs "rarely or none of the time," respectively. Among women with more extensive social networks, estimated probabilities were 0.20 and 0.21, respectively. CONCLUSIONS: Family-based adverse childhood experiences are related to lower urinary tract symptoms/impact vs bladder health in adulthood. Additional research is needed to corroborate the potentially attenuating effect of social networks.

Discrimination and bladder health among women in the CARDIA cohort study: Life course and intersectionality perspectives.

OBJECTIVE: This study examines whether discriminatory experiences are associated with lower urinary tract symptoms (LUTS) and their impact among 972 women in the Coronary Artery Risk Development in Young Adults (CARDIA) cohort study, which recruited participants from 4 cities in the United States. METHOD: Exposure to discrimination was assessed 3 times (1992-93, 2000-01, 2010-11) and averaged across assessments. Participants separately reported whether they experienced discrimination on the basis of their gender, race or color, and socioeconomic position or social class. For each social identity, discrimination was assessed in 6-7 settings (e.g., when getting a job, medical care, or housing). At different time points, women who reported discriminatory experiences for a given social identity were asked how frequently the discrimination occurred and how stressful experience(s) were. Following the 2010-11 assessment, data on LUTS and their impact were collected. Women were classified into bladder health versus mild, moderate, or severe symptoms/impact clusters. RESULTS: More Black than White women reported discriminatory experiences across all social identities and most settings. Perceived stress of discriminatory experiences did not differ between Black and White women. In analyses stratified by race and social identity, White women reported LUTS/impact with discriminatory experiences in more settings, more frequent discriminatory experiences across settings, and each additional social identity for which discrimination was experienced. Black women reported LUTS/impact with more frequent discriminatory experiences across settings. For Black women, greater perceived stress of both gender and race discrimination were associated with LUTS/impact. For White women, only greater perceived stress of race discrimination was associated with LUTS/impact. CONCLUSIONS: This is one of the first studies to examine discrimination in relation to LUTS/impact. Additional research is needed to better understand differences in how discriminatory experiences based on potentially intersecting identities may be related to bladder health among women.

Cognitive function and bladder health among midlife adult women in the Coronary Artery Risk Development in Young Adults (CARDIA) study.

OBJECTIVE: The aim of this study was to examine whether different aspects of women's cognitive function are associated with lower urinary tract symptoms (LUTS) and their impact. METHODS: In 2010-2011, women aged 42 to 57 years in the Coronary Artery Risk Development in Young Adults study completed different tests of cognitive function, including the Digit Symbol Substitution Test, Rey Auditory Verbal Learning Test, and Stroop test. Two years later, data on LUTS and their impact were collected. LUTS/impact, a four-level composite variable ranging from bladder health to mild, moderate, and severe LUTS/impact, was regressed on each cognitive test separately, as well as a cognitive function composite variable. The analytic sample was composed of 1,021 women with complete data. RESULTS: When adjusting for sociodemographic variables (age, race, education) and gynecologic/obstetric variables (parity, menopausal status, hysterectomy, hormonal use), better performance on the cognitive function composite and Digit Symbol Substitution Test were both associated with lower odds of membership to a more severe LUTS/impact category (odds ratio, 0.90 [95% confidence interval, 0.83-0.98] and 0.89 [95% confidence interval, 0.82-0.97], respectively). These associations became nonsignificant when additionally adjusting for mechanisms that might explain an association between cognitive function and LUTS/impact, including health behaviors and health conditions that may covary with cerebral and peripheral vascular health and cognitive function. CONCLUSIONS: In this sample of midlife adult women, a modest association was found between better cognitive function and lower likelihood of LUTS/impact. Longitudinal studies are needed to further investigate the association between cognitive function and LUTS/impact, as well as potential explanatory mechanisms, particularly as women age and cognitive function varies to a greater degree.

Interpersonal Stressors and Resources for Support: Associations with Lower Urinary Tract Symptoms and Impact Among Women.

Background: This study utilizes Coronary Artery Risk Development in Young Adults (CARDIA) data to examine whether women's perceived emotional support and interpersonal stressors are associated with lower urinary tract symptoms (LUTS) and their impact on quality of life. Materials and Methods: Emotional support was assessed at baseline/year 0 (1985-86), year 2 (1987-88), year 15 (2000-01), and year 20 (2005-06); interpersonal stressors were assessed at years 15 and 20. In 2012-13, LUTS and impact were assessed. LUTS/impact category (a composite variable ranging from bladder health to mild, moderate, and severe LUTS/impact) was regressed on trajectory groups of emotional support from years 0 to 20. Separately, LUTS/impact was regressed on mean emotional support and interpersonal stressors across years 15-20. Analyses were adjusted for age, race, education, and parity (n = 1104). Results: In comparison to women whose support trajectory from years 0 to 20 was consistently high, women whose support decreased from high to low had over twice the odds (odds ratio [OR] = 2.72; 95% confidence interval [CI] = 1.76-4.20) of being classified into a more burdensome LUTS/impact category. Mean support and interpersonal stressors across years 15-20 were independently associated with lower odds (OR = 0.59; 95% CI = 0.44-0.77) and greater odds (OR = 1.52; 95% CI = 1.19-1.94), respectively, of being classified into a more burdensome LUTS/impact category. Conclusions: In the CARDIA cohort, quality of women's interpersonal relationships, assessed between 1985-86 and 2005-06, was associated with LUTS/impact assessed in 2012-13. Additional research collecting LUTS/impact data at multiple time points is needed to test potential bidirectional associations of emotional support and interpersonal stressors with LUTS/impact, as well as potential mechanisms of association.

Trajectories of depressive symptoms over 20 years and subsequent lower urinary tract symptoms and impact among women.

OBJECTIVE: The aim of the study is to examine the association between depressive symptoms and subsequent lower urinary tract symptoms (LUTS) and impact (a composite outcome) among women (N = 1,119) from the Coronary Artery Risk Development in Young Adults study. METHODS: The Center for Epidemiologic Studies-Depression Scale (CES-D) was administered in 1990-1991 and every 5 years through 2010-2011. In 2012-2013, LUTS and impact data were collected for the first time. Accumulation of risk was examined in the following three ways: (1) mean CES-D score across 20 years (5 observations); (2) depressive symptom trajectory group, determined by group-based trajectory modeling; and (3) intercepts and slopes obtained from women's individual CES-D score trajectories through two-stage mixed effects modeling. For each approach, ordinal logistic regression analyses examined odds of having "greater LUTS/impact" for each unit change in a depressive symptom variable. RESULTS: (1) With each one-unit increase in mean CES-D score over the 20-year period, women were 9% more likely to report greater LUTS/impact (odds ratio [OR] = 1.09, 95% CI = 1.07-1.11). (2) In comparison with women with consistently low depressive symptoms, women with consistently threshold depression or consistently high depressive symptoms were twice (OR = 2.07, 95% CI = 1.59-2.69) and over five times (OR = 5.55, 95% CI = 3.07-10.06) as likely, respectively, to report greater LUTS/impact. (3) Women's individual symptom intercept and slope interacted. Increases in depressive symptoms across 20 years (greater slopes) were associated with greater LUTS/impact when women's initial CES-D score (intercept) was in the moderate-to-high range relative to the sample. CONCLUSIONS: Depressive symptoms over 20 years, examined with different degrees of nuance, were consistently associated with subsequently measured LUTS and impact.

Mutational survivorship bias: The case of PNKP.

The molecular function of a protein relies on its structure. Understanding how variants alter structure and function in multidomain proteins is key to elucidate the generation of a pathological phenotype. However, one may fall into the logical bias of assessing protein damage only based on the variants that are visible (survivorship bias), which can lead to partial conclusions. This is the case of PNKP, an important nuclear and mitochondrial DNA repair enzyme with both kinase and phosphatase function. Most variants in PNKP are confined to the kinase domain, leading to a pathological spectrum of three apparently distinct clinical entities. Since proteins and domains may have a different tolerability to variation, we evaluated whether variants in PNKP are under survivorship bias. Here, we provide the evidence that supports a higher tolerance in the kinase domain even when all variants reported are deleterious. Instead, the phosphatase domain is less tolerant due to its lower variant rates, a higher degree of sequence conservation, lower dN/dS ratios, and the presence of more disease-propensity hotspots. Together, our results support previous experimental evidence that demonstrated that the phosphatase domain is functionally more necessary and relevant for DNA repair, especially in the context of the development of the central nervous system. Finally, we propose the term "Wald's domain" for future studies analyzing the possible survivorship bias in multidomain proteins.