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BACKGROUND: Recent reports suggest that racial differences in breast cancer incidence rates have decreased. We examined whether these findings apply to breast cancer mortality while considering age, period, and cohort influences on both absolute and relative measures of breast cancer mortality. METHODS: Using publicly available datasets (CDC Wonder, Human Mortality Database), we developed an age-period-cohort model of breast cancer mortality and breast cancer deaths as a proportion of all deaths during 1968–2019 among all women and by five race/ethnicity groups with sufficient numbers for estimation: Hispanic (all races), American Indian/Alaska Native and Asian/Pacific Islanders (regardless of ethnicity), non-Hispanic Black, and non-Hispanic White. RESULTS: Initially increasing after 1968, age-adjusted breast cancer mortality rates have decreased among all racial/ethnic groups since 1988. The age-adjusted percent of all deaths due to breast cancer also has been declining for non-Hispanic White women since about 1990 while increasing or holding steady for other race/ethnic groups. In 2019, the age-adjusted percent of deaths due to breast cancer for women was highest for Asian/Pacific Islanders (5.6%) followed by non-Hispanic Black (4.5%), Hispanic (4.4%), non-Hispanic White (4.1%), and American Indian/Alaska Native women (2.6%). CONCLUSIONS: Breast cancer mortality disparities are now greater on both relative and absolute scales for non-Hispanic Black women, and using the relative scale for Asian/Pacific Islander and Hispanic women, compared with non-Hispanic White women for the first time in 50 years.

PURPOSE: Physical activity is important for healthy cancer survivorship, yet many endometrial cancer survivors do not participate in recommended muscle-strengthening activity. The purpose of this study was to determine the feasibility of home-based muscle strengthening activity in endometrial cancer survivors. METHODS: Forty post-treatment endometrial cancer survivors were enrolled in a randomized trial, of twice-weekly home-based strength exercise versus wait-list control. The intervention included educational materials, exercise equipment (dumbbells, resistance bands), and support/feedback via video coaching sessions. Participants completed the exercises twice per week for 10 weeks, with a 5-week follow-up period. Feasibility was measured by program adherence, as well as safety of and satisfaction with the study. RESULTS: On average, participants were 60.9 years old (SD = 8.7), had a BMI of 39.9 kg/m(2) (SD = 15.2), and were 2.9 years (SD = 1.2) since diagnosis. The majority (83%) had stage I disease at diagnosis. Seventy-five percent adhered to the exercise prescription of twice/week, with 85% of participants missing fewer than 3 of the workouts. Forty percent of participants continued workouts during the 5-week follow-up. Participants were highly satisfied with intervention. No injuries or adverse everts occurred. CONCLUSION: This home-based program was feasible in endometrial cancer survivors. While adherence was measured, future research should focus on long-term maintenance of exercise and should explore progressions and modifications of exercises at a distance for various abilities. IMPLICATIONS FOR CANCER SURVIVORS: Muscle strengthening activities are recommended for all cancer survivors. This study shows that a home-based muscle strengthening exercise is feasible in endometrial cancer survivors.

Background: The evidence base regarding validity of wearable fitness trackers for assessment and/or modification of physical activity behavior is evolving. Accurate assessment of moderate- to vigorous-intensity physical activity (MVPA) is important for measuring adherence to physical activity guidelines in the United States and abroad. Therefore, this systematic review synthesizes the state of the validation literature regarding wearable trackers and MVPA.Methods: A systematic search of the PubMed, Scopus, SPORTDiscus, and Cochrane Library databases was conducted through October 2019 (PROSPERO registration number: CRD42018103808). Studies were eligible if they reported on the validity of MVPA and used devices from Fitbit, Apple, or Garmin released in 2012 or later or available on the market at the time of review. A meta-analysis was conducted on the correlation measures comparing wearables with the ActiGraph.Results: Twenty-two studies met the inclusion criteria; all used a Fitbit device; one included a Garmin model and no Apple-device studies were found. Moderate to high correlations (.7–.9) were found between MVPA from the wearable tracker versus criterion measure (ActiGraphn = 14). Considerable heterogeneity was seen with respect to the specific definition of MVPA for the criterion device, the statistical techniques used to assess validity, and the correlations between wearable trackers and ActiGraph across studies.Conclusions: There is a need for standardization of validation methods and reporting outcomes in individual studies to allow for comparability across the evidence base. Despite the different methods utilized within studies, nearly all concluded that wearable trackers are valid for measuring MVPA.

OBJECTIVES This pilot trial tested the effect of adding a multi-level, technology-based physical activity intervention module to a standard survivorship care plan for breast and colorectal cancer survivors. The objective of this analysis was to determine whether the physical activity module improved health-related quality of life, sleep, and factors key to lasting behavior change (eg, social support, self-efficacy). METHODS Breast and colorectal cancer survivors (n = 50) were enrolled alongside a support partner. Survivors were assigned to receive a standard survivorship care plan either alone or augmented by a 12-week multi-component physical activity module. The module included a Fitbit tracker (with the physical activity data integrated into the electronic health record for clinician review) and customized email feedback. Physical activity was measured using the ActiGraph GT3X+. Psychosocial outcomes included the SF-36, FACT, ISEL, PROMIS sleep measures, and physical activity beliefs. Data were analyzed using linear mixed modeling. RESULTS Cancer survivors were aged 54.4 ± 11.2 years and were 2.0 ± 1.5 years from diagnosis. Relative to comparison, the intervention was associated with moderate-to-large improvements in physical health (effect size: d = 0.39, 95% CI = 0.0, 0.78), mental health (d = 0.59, 95% CI = 0.19, 0.99), sleep impairment (d = 0.62, 95% CI = -1.02, -0.22), and exercise self-efficacy (d = 0.60, 95% CI = 0.20, 1.0). CONCLUSIONS The intervention delivered meaningful improvements in survivors' quality of life, social support, and sleep impairment. If replicated in a larger sample, adding a technology-supported physical activity module to survivorship care plans may be a practical strategy for supporting healthy survivorship. TRIAL REGISTRATION ClinicalTrials.gov#: NCT02677389.

Background: African ancestry is associated with a higher prevalence and greater severity of asthma than European ancestries, yet genetic studies of the most common locus associated with childhood-onset asthma, 17q12–21, in African Americans have been inconclusive. The aim of this study was to leverage both the phenotyping of the Children's Respiratory and Environmental Workgroup (CREW) birth cohort consortium, and the reduced linkage disequilibrium in African Americans, to fine map the 17q12–21 locus. Methods: We first did a genetic association study and meta-analysis using 17q12–21 tag single-nucleotide polymorphisms (SNPs) for childhood-onset asthma in 1613 European American and 870 African American children from the CREW consortium. Nine tag SNPs were selected based on linkage disequilibrium patterns at 17q12–21 and their association with asthma, considering the effect allele under an additive model (0, 1, or 2 effect alleles). Results were meta-analysed with publicly available summary data from the EVE consortium (on 4303 European American and 3034 African American individuals) for seven of the nine SNPs of interest. Subsequently, we tested for expression quantitative trait loci (eQTLs) among the SNPs associated with childhood-onset asthma and the expression of 17q12–21 genes in resting peripheral blood mononuclear cells (PBMCs) from 85 African American CREW children and in upper airway epithelial cells from 246 African American CREW children; and in lower airway epithelial cells from 44 European American and 72 African American adults from a case-control study of asthma genetic risk in Chicago (IL, USA). Findings: 17q12–21 SNPs were broadly associated with asthma in European Americans. Only two SNPs (rs2305480 in gasdermin-B [GSDMB] and rs8076131 in ORMDL sphingolipid biosynthesis regulator 3 [ORMDL3]) were associated with asthma in African Americans, at a Bonferroni-corrected threshold of p

Introduction:Translating complex behavior change interventions into practice can be accompanied by a loss of fidelity and effectiveness. We present the evaluation of two sequential phases of implementation of a complex evidence-based community workshop to reduce falls, using the Replicating Effective Programs Framework. Between the two phases, workshop training and delivery were revised to improve fidelity with key elements.Methods:Stepping On program participants completed a questionnaire at baseline (phase 1: n = 361; phase 2: n = 2219) and 6 months post-workshop (phase 1: n = 232; phase 2: n = 1281). Phase 2 participants had an additional follow-up at 12 months (n = 883). Outcomes were the number of falls in the prior 6 months and the Falls Behavioral Scale (FaB) score.Results:Workshop participation in phase 1 was associated with a 6% reduction in falls (RR = 0.94, 95% CI 0.74–1.20) and a 0.14 improvement in FaB score (95% CI, 0.11– 0.18) at 6 months. Workshop participation in phase 2 was associated with a 38% reduction in falls (RR = 0.62, 95% CI 0.57–0.68) and a 0.16 improvement in FaB score (95% CI 0.14–0.18) at 6 months, and a 28% reduction in falls (RR = 0.72, 95% CI 0.65–0.80) and a 0.19 score improvement in FaB score (95% CI 0.17–0.21) at 12-month follow-up.Conclusions:Effectiveness can be maintained with widespread dissemination of a complex behavior change intervention if attention is paid to fidelity of key elements. An essential role for implementation science is to ensure effectiveness as programs transition from research to practice.

PURPOSE: Endometrial cancer is strongly linked to obesity and inactivity; however, increased physical activity has important benefits even in the absence of weight loss. Resistance (strength) training can deliver these benefits; yet few women participate in resistance exercise. The purpose of this study was to describe both physiological and functional changes following a home-based strength training intervention. METHODS: Forty post-treatment endometrial cancer survivors within 5 years of diagnosis were enrolled in a pilot randomized trial, comparing twice-weekly home-based strength exercise to wait list control. Participants conducted the exercises twice per week for 10 supervised weeks with 5 weeks of follow-up. Measures included DXA-measured lean mass, functional fitness assessments, blood biomarkers, and quality of life outcomes. RESULTS: On average, participants were 60.9 years old (SD = 8.7) with BMI of 39.9 kg/m(2) (SD = 15.2). At baseline, participants had 51.2% (SD = 6.0) body fat, which was not different between groups. Improvements were seen in the 30-s chair sit to stand (d = .99), the 30-s arm curl (d = .91), and the 8-ft up-and-go test (d = .63). No changes were measured for HbA1c or C-reactive protein. No changes were observed for flexibility (chair sit and reach, back scratch tests), 6-min walk test, maximum handgrip test, anxiety, depression, fatigue, or self-efficacy for exercise. CONCLUSIONS: Home-based muscle-strengthening exercise led to favorable and clinically relevant improvements in 3 of 7 physical function assessments. Physical function, body composition, blood biomarkers, and patient-reported outcomes were feasible to measure. These fitness improvements were observed over a relatively short time frame of 10 weeks.

BACKGROUND High adolescent gun-related mortality, gun violence, pro-gun policies, white supremacy, and the long-term socioeconomic and other effects of racial oppression are intricately linked in the United States. Racist prejudice depicts male individuals of color as more prone to criminality than white male individuals. We described long-term patterns of weapon carrying in US schools among non-Hispanic (NH) white, NH Black/African American, and Hispanic boys, hypothesizing that in contrast to racist stereotypes, boys of color did not bring weapons into schools more often than NH white boys in recent years. METHODS We conducted a time series analysis using 1993–2019 Youth Risk Behavior Surveillance System data comparing boys’ self-reported weapon carrying in a nationally representative sample of US high schools by race and/or ethnicity, age, and self-reported experience of safety and violence at school. RESULTS Weapon carrying in schools has declined among all boys. Comparing all schools, we found no significant differences in weapon carrying (4%–5%) by race and/or ethnicity in 2017 and 2019. Boys who reported experiencing violence or feeling unsafe at school were at least twice as likely to bring a weapon into school, and such negative experiences were more common among boys of color (8%–12%) than among NH white boys (4%–5%). In schools perceived as safer, NH white boys have been more likely to bring weapons into schools than NH Black/African American or Hispanic boys in the past 20 years. CONCLUSIONS Our findings contradict racist prejudice with regard to weapon carrying in schools, particularly in more favorable school environments. Making schools safer may reduce weapon carrying in schools where weapon carrying is most common.

BackgroundSchools are primary venues of influenza amplification with secondary spread to communities. We assessed K-12 student absenteeism monitoring as a means for early detection of influenza activity in the community.Materials and MethodsBetween September 2014 and March 2020, we conducted a prospective observational study of all-cause (a-TOT), illness-associated (a-I), and influenza-like illness–associated (a-ILI) absenteeism within the Oregon School District (OSD), Dane County, Wisconsin. Absenteeism was reported through the electronic student information system. Students were visited at home where pharyngeal specimens were collected for influenza RT-PCR testing. Surveillance of medically-attended laboratory-confirmed influenza (MAI) occurred in five primary care clinics in and adjoining OSD. Poisson general additive log linear regression models of daily counts of absenteeism and MAI were compared using correlation analysis.FindingsInfluenza was detected in 723 of 2,378 visited students, and in 1,327 of 4,903 MAI patients. Over six influenza seasons, a-ILI was significantly correlated with MAI in the community (r = 0.57; 95% CI: 0.53—0.63) with a one-day lead time and a-I was significantly correlated with MAI in the community (r = 0.49; 0.44-0.54) with a 10-day lead time, while a-TOT performed poorly (r = 0.27; 0.21—0.33), following MAI by six days.DiscussionSurveillance using cause-specific absenteeism was feasible and performed well over a study period marked by diverse presentations of seasonal influenza. Monitoring a-I and a-ILI can provide early warning of seasonal influenza in time for community mitigation efforts.

Purpose To evaluate the relationship of retinal layer thickness with age and age-related macular degeneration (AMD) in the Carotenoids in Age-Related Eye Disease Study 2. Methods Total retinal thickness within the macular area, and individual layer thickness was determined for CAREDS2 participants (n = 906 eyes, 473 women) from the Women's Health Initiative using Heidelberg optical coherence tomography (OCT). Mean measurements within the OCT grid were compared across age tertiles (69–78, 78–83, and 83–101 years) and AMD outcomes. Results Mean retinal thickness in the central circle, inner ring, and outer ring were 277 ± 34 µm, 326 ± 20 µm, and 282 ± 15 µm, respectively. Thickness did not vary by age in the central circle, but decreased with age in the inner and outer circles (P ≤ 0.004). Specifically, ganglion cell (GCL), inner plexiform, and outer nuclear (ONL) layer thickness decreased with age (P ≤ 0.003). Age-adjusted retinal thickness in all three circles did not vary by AMD outcomes (486 without AMD and 413 with AMD). However, individual layers showed changes with GCL and photoreceptor thinning and retinal pigment epithelial thicknening in eyes with late AMD. After controlling for age and AMD, higher ONL thickness was associated with better visual acuity. Conclusions In this cohort of older women, a decrease in perifoveal thickness was associated with increasing age, particularly in the inner retinal layers. Variabilty in thickness in AMD eyes was primarily due to outer retinal layers. Among all retinal layers, the ONL plays an important role in preserving visual acuity. Translational Relevance The study provides a deeper understanding of age related changes to the retinal layers and their effect on visual loss.

Purpose To examine the relationships of retinal vessel geometric characteristics (RVGCs) to the incidence and progression of diabetic retinopathy (DR). Design Observational, prospective cohort study. Participants Nine hundred ninety-six persons with type 1 diabetes mellitus (T1DM) and 1370 persons with type 2 diabetes mellitus (T2DM) seen at a baseline examination who were eligible for follow-up examinations at subsequent 5-year intervals. A total of 3846 person-interval data from these follow-up examinations are the basis for the analyses. Methods Diabetic retinopathy and macular edema were assessed by grading of 30° stereoscopic color fundus photographs. Retinal vessel geometric characteristics were assessed using the Singapore I Vessel Assessment program from a digitized copy of 1 of the field 1 fundus photographs obtained at baseline and follow-up. Main Outcome Measures The 5-year incidence of any DR, progression of DR, and incidence of proliferative diabetic retinopathy (PDR) and clinically significant macular edema (CSME) in right eyes. Results Incident DR occurred in 45%, progression in 32%, PDR in 10%, and CSME in 5%. While adjusting for glycated hemoglobin, duration of diabetes, and other factors, retinal arteriolar simple tortuosity was associated significantly with the incidence of any DR (odds ratio [OR], 1.17; 95% confidence interval [CI], 1.01–1.35). Retinal venular branching angle was associated significantly with progression of DR (OR, 1.18; 95% CI, 1.03–1.36), retinal venular curvature tortuosity was associated significantly with the incidence of PDR (OR, 1.15; 95% CI, 1.01–1.30), and retinal venular branching angle (OR, 1.41; 95% CI, 1.10–1.82) was associated significantly with the incidence of CSME. There were no significant associations of other RVGCs with any of the DR outcomes in the full multivariate model. Inclusion of all possible RVGCs did not improve the predictive value of the models that already included retinal vessel diameter and baseline DR severity level. Conclusions Retinal vessel geometric characteristics of the retinal venules were associated with progression of DR; however, most of the RVGCs measured from digitized fundus photographs added little to the assessment of risk of incidence and progression of DR when other risk factors were considered in T1DM and T2DM.

Spatial and spatio-temporal cluster detection are important tools in public health and many other areas of application. Cluster detection can be approached as a multiple testing problem, typically using a space and time scan statistic. We recast the spatial and spatio-temporal cluster detection problem in a high-dimensional data analytical framework with Poisson or quasi-Poisson regression with the Lasso penalty. We adopt a fast and computationally-efficient method using a novel sparse matrix representation of the effects of potential clusters. The number of clusters and tuning parameters are selected based on (quasi-)information criteria. We evaluate the performance of our proposed method including the false positive detection rate and power using a simulation study. Application of the method is illustrated using breast cancer incidence data from three prefectures in Japan.

Rationale: Rhinovirus (RV) C can cause asymptomatic infection and respiratory illnesses ranging from the common cold to severe wheezing. Objectives: To identify how age and other individual-level factors are associated with susceptibility to RV-C illnesses. Methods: Longitudinal data from the COAST (Childhood Origins of Asthma) birth cohort study were analyzed to determine relationships between age and RV-C infections. Neutralizing antibodies specific for RV-A and RV-C (three types each) were determined using a novel PCR-based assay. Data were pooled from 14 study cohorts in the United States, Finland, and Australia, and mixed-effects logistic regression was used to identify factors related to the proportion of RV-C versus RV-A detection. Measurements and Main Results: In COAST, RV-A and RV-C infections were similarly common in infancy, whereas RV-C was detected much less often than RV-A during both respiratory illnesses and scheduled surveillance visits (P

Background Studies indicate that the nasal microbiome may correlate strongly with the presence or future risk of childhood asthma. Objectives In this study, we tested whether developmental trajectories of the nasopharyngeal microbiome in early life and the composition of the microbiome during illnesses were related to risk of childhood asthma. Methods Children participating in the Childhood Origins of Asthma study (n=285) provided nasopharyngeal mucus samples in the first two years of life, during routine healthy study visits (2, 4, 6, 9, 12, 18 and 24 months of age) and episodes of respiratory illnesses, which were analyzed for respiratory viruses and bacteria. We identified developmental trajectories of early-life microbiome composition, as well as predominant bacteria during respiratory illnesses, and correlated these with presence of asthma at 6, 8, 11, 13 and 18 years of age. Results Of the four microbiome trajectories identified, a Staphylococcus-dominant microbiome in the first 6 months of life was associated with increased risk of recurrent wheezing by age 3 years and asthma that persisted throughout childhood. In addition, this trajectory was associated with the early onset of allergic sensitization. During wheezing illnesses, detection of rhinoviruses and predominance of Moraxella were associated with asthma that persisted throughout later childhood. Conclusion In infancy, the developmental composition of the microbiome during healthy periods and the predominant microbes during acute wheezing illnesses are both associated with the subsequent risk of developing persistent childhood asthma. Clinical Implication Identifying factors that promote early colonization with S. aureus may lead to future interventional studies to prevent childhood asthma., Capsule summary: In a birth cohort study, early colonization of the upper airway with Staphylococcus aureus and detection of rhinoviruses and Moraxella catarrhalis during illnesses were associated with subsequent childhood asthma.

OBJECTIVES: We examined the association of exposure to maternal depression during year 2 of a child’s life with future child problem behavior. We conducted a secondary analysis to investigate whether race/ethnicity is a moderator of this relationship. METHODS: We used Fragile Families and Child Well-Being Study data (age 3 N=3288 and 49% Black, 26% Hispanic, 22% non-Hispanic White; age 5 N=3001 and 51% Black, 25% Hispanic, 21% non-Hispanic White; age 9 N=3630 and 50% Black, 25% Hispanic, 21% non-Hispanic White) and ordinal logistic regression to model problem behavior at ages 3, 5, and 9 on maternal depression status during year 2. RESULTS: At age 9, children whose mother was depressed during year 2 were significantly more likely to have higher internalizing (AOR=1.92, 95% CI: 1.42,2.61) and externalizing (AOR=1.65, 95% CI: 1.10,2.48) problem behavior scores. In our secondary analysis, race/ethnicity did not have moderating effects, potentially due to a limitation of the data that required use of maternal self-reported race/ethnicity as a proxy for child race/ethnicity. Conclusions for Practice: Exposure to maternal depression after the prenatal and perinatal periods may have a negative association with children’s behavioral development through age 9. Interventions that directly target maternal depression during this time should be developed. Additional research is needed to further elucidate the role of race/ethnicity in the relationship between maternal depression and child problem behavior.

Objectives We aimed to estimate the association between Medicaid unbundling of payment for long-acting reversible contraceptives (LARC) from the global delivery fee and immediate postpartum (IPP) LARC provision, in a state outside a select group of early-adopters. We also examine the potential moderating roles of hospital academic affiliation and Catholic status on the association between unbundling and IPP LARC provision. Methods We used a pre–post design to examine the association between unbundling and IPP LARC provision. We observed Medicaid-covered childbirth deliveries in Wisconsin hospitals between January 2016 and December 2017 (n = 45,200) in the State Inpatient Database from the Agency for Healthcare Research and Quality's Healthcare Cost and Utilization Project. We conducted multivariate regressions using generalized linear mixed models. Results From 2016 to 2017, IPP LARC provision increased from 0.28% to 0.44% of deliveries (p = .003). In our adjusted model, IPP LARC provision was 1.55 times more likely in the post–period versus the pre-period (95% confidence interval, 1.12–2.13). Both before and after unbundling, IPP LARC provision was significantly more common in academic versus nonacademic settings and was exceedingly rare in Catholic institutions. Conclusions In contrast with many early adopting states, in this later adopting state, Wisconsin Medicaid's unbundling of LARC from the global fee did not meaningfully change the rates of IPP LARC provision. These results indicate that delivery hospital characteristics are strong correlates of access to IPP LARC and suggest the need for interventions—perhaps outside of the inpatient setting—to ensure that patients can access desired contraceptive methods promptly postpartum.

PURPOSE: Higher mortality after a breast cancer diagnosis has been observed among women who are obese. We investigated the relationships between body mass index (BMI) and all-cause or breast cancer-specific mortality after a diagnosis of locoregional breast cancer. METHODS: Women diagnosed in 2004 with AJCC Stage I, II, or III breast cancer (n = 5394) were identified from a population-based National Program of Cancer Registries (NPCR) patterns of care study (POC-BP) drawing from registries in seven U.S. states. Differences in overall and breast cancer-specific mortality were investigated using Cox proportional hazards regression models adjusting for demographic and clinical covariates, including age- and stage-based subgroup analyses. RESULTS: In women 70 or older, higher BMI was associated with lower overall mortality (HR for a 5 kg/m(2) difference in BMI = 0.85, 95% CI 0.75–0.95). There was no significant association between BMI and overall mortality for women under 70. BMI was not associated with breast cancer death in the full sample, but among women with Stage I disease; those in the highest BMI category had significantly higher breast cancer mortality (HR for BMI ≥ 35 kg/m(2) vs. 18.5–24.9 kg/m(2) = 4.74, 95% CI 1.78–12.59). CONCLUSIONS: Contrary to our hypothesis, greater BMI was not associated with higher overall mortality. Among older women, BMI was inversely related to overall mortality, with a null association among younger women. Higher BMI was associated with breast cancer mortality among women with Stage I disease, but not among women with more advanced disease.

Objective. Breast cancer simulation models must take changing mortality rates into account to evaluate the potential impact of cancer control interventions. We estimated mortality rates due to breast cancer and all other causes combined to determine their impact on overall mortality by year, age, and birth cohort. Methods. Based on mortality rates from publicly available datasets, an age-period-cohort model was used to estimate the proportion of deaths due to breast cancer for US women aged 0 to 119 years, with birth years 1900 to 2000. Breast cancer mortality was calculated as all-cause mortality multiplied by the proportion of deaths due to breast cancer; other-cause mortality was the difference between all-cause and breast cancer mortality. Results. Breast cancer and other-cause mortality rates were higher for older ages and birth cohorts. The percent of deaths due to breast cancer increased across birth cohorts from 1900 to 1940 then decreased. Among 50-year-old women, in the 1920 birth cohort, 52 (9.9%) of 100,000 deaths (95% CI, 9.8% to 10.1%) were attributed to breast cancer whereas 476 of 100,000 were due to other causes; in the 1960 birth cohort, 22 (8.5%) of 100,000 deaths (95% CI, 8.3% to 8.7%) were attributed to breast cancer with 242 of 100,000 deaths due to other causes. The percentage of all deaths due to breast cancer was highest (4.1% to 12.9%) for women in their 40s and 50s for all birth cohorts. Conclusions. This study offers evidence that advances in breast cancer screening and treatment have reduced breast cancer mortality for women across the age spectrum, and provides estimates of age-, year- and birth cohort-specific competing mortality rates for simulation models. Other-cause mortality estimates are important in these models because most women die from causes other than breast cancer.

The University of Wisconsin Breast Cancer Epidemiology Simulation Model (UWBCS), also referred to as Model W, is a discrete-event microsimulation model that uses a systems engineering approach to replicate breast cancer epidemiology in the US over time. This population-based model simulates the lifetimes of individual women through 4 main model components: breast cancer natural history, detection, treatment, and mortality. A key feature of the UWBCS is that, in addition to specifying a population distribution in tumor growth rates, the model allows for heterogeneity in tumor behavior, with some tumors having limited malignant potential (i.e., would never become fatal in a woman’s lifetime if left untreated) and some tumors being very aggressive based on metastatic spread early in their onset. The model is calibrated to Surveillance, Epidemiology, and End Results (SEER) breast cancer incidence and mortality data from 1975 to 2010, and cross-validated against data from the Wisconsin cancer reporting system. The UWBCS model generates detailed outputs including underlying disease states and observed clinical outcomes by age and calendar year, as well as costs, resource usage, and quality of life associated with screening and treatment. The UWBCS has been recently updated to account for differences in breast cancer detection, treatment, and survival by molecular subtypes (defined by ER/HER2 status), to reflect the recent advances in screening and treatment, and to consider a range of breast cancer risk factors, including breast density, race, body-mass-index, and the use of postmenopausal hormone therapy. Therefore, the model can evaluate novel screening strategies, such as risk-based screening, and can assess breast cancer outcomes by breast cancer molecular subtype. In this article, we describe the most up-to-date version of the UWBCS.

Due to limitations in the ability to identify non-progressive disease, ductal carcinoma in situ (DCIS) is usually managed similarly to localized invasive breast cancer. We used simulation modeling to evaluate the potential impact of a hypothetical test that identifies non-progressive DCIS. A discrete-event model simulated a cohort of U.S. women undergoing digital screening mammography. All women diagnosed with DCIS underwent the hypothetical DCIS prognostic test. Women with test results indicating progressive DCIS received standard breast cancer treatment and a decrement to quality of life corresponding to the treatment. If the DCIS test indicated non-progressive DCIS, no treatment was received and women continued routine annual surveillance mammography. A range of test performance characteristics and prevalence of non-progressive disease were simulated. Analysis compared discounted quality-adjusted life years (QALYs) and costs for test scenarios to base-case scenarios without the test. Compared to the base case, a perfect prognostic test resulted in a 40% decrease in treatment costs, from $13,321 to $8005 USD per DCIS case. A perfect test produced 0.04 additional QALYs (16 days) for women diagnosed with DCIS, added to the base case of 5.88 QALYs per DCIS case. The results were sensitive to the performance characteristics of the prognostic test, the proportion of DCIS cases that were non-progressive in the model, and the frequency of mammography screening in the population. A prognostic test that identifies non-progressive DCIS would substantially reduce treatment costs but result in only modest improvements in quality of life when averaged over all DCIS cases.

Purpose To determine if skin intrinsic fluorescence (SIF), a noninvasive measure of advanced glycation endproducts and oxidative stress in skin is associated with AMD. Methods SIF was measured with the SCOUT DS skin fluorescence spectrometer in a cross-sectional cohort study of 969 persons aged 68 to 102 years from the 1181 who participated in the 25-year follow-up examination in the Beaver Dam Eye Study (BDES) in 2014 to 2016. The SCOUT DS skin fluorescence spectrometer uses five light-emitting diodes, centered at 375 nm to 456 nm. AMD was assessed by grading of digital color 45° stereoscopic fundus photographs of the macula using the Wisconsin Age-Related Maculopathy grading scheme. Analyses included logistic regression with generalized estimating equations to account for correlation between the eyes of a person. Results There were data for 1827 eyes for analyses. Early AMD was present in 22% and late AMD in 4% of the eyes. While adjusting for age, sex, smoking status, and history of cardiovascular disease, there were no significant associations of any SIF measure with any AMD or exudative AMD. SIF01 (odds ratio per 1 SD difference on the log scale, 95% confidence interval) (1.66, 1.00-2.74, P = 0.05) and SIF03 (1.81, 1.16-2.81, P = 0.008) were associated with geographic atrophy. Conclusions There was a suggestive relationship of two SIF measures, SIF01 and SIF03, using different correction factors from the excitation centered at 375 nm, with the prevalence of geographic atrophy in the BDES. Longitudinal follow-up is indicated to assess a temporal relationship.

Funding has been provided by a USDA Cooperative State Research, Education and Extension Service (CSREES) McIntire-Stennis project. We thank the School of Natural Resources and Agricultural Sciences, University of Alaska Fairbanks, for the development and maintenance of the Cooperative Alaska Forest Inventory, and thank the Global Forest Biodiversity Initiative (GFBI) for establishing data-sharing protocols and standards for international collaborative research projects. We also thank Thomas Malone for his insights on Alaska boreal forest.

To examine factors influencing primary care provider (PCP) adoption of CT colonography (CTC) for colorectal cancer (CRC) screening. We performed a retrospective cohort study linking electronic health record (EHR) data with PCP survey data. Patients were eligible for inclusion if they were not up-to-date with CRC screening and if they had CTC insurance coverage in the year prior to survey administration. PCPs were included if they had at least one eligible patient in their panel and completed the survey (final sample N = 95 PCPs; N = 6245 patients). Survey data included perceptions of CRC screening by any method, as well as CTC specifically. Multivariate logistic regression estimated odds ratios and 95% confidence intervals for PCP and clinic predictors of CRC screening by any method and screening with CTC. Substantial variation in CTC use was seen among PCPs and clinics (range 0–16% of CRC screening). Predictors of higher CTC use were PCP perceptions that CTC is effective in reducing CRC mortality, higher number of perceived advantages to screening with CTC, and Internal Medicine specialty. Factors not associated with CTC use were PCP perceptions of less organizational capacity to meet demand for colonoscopy, number of perceived disadvantages to screening with CTC, PCP age and gender, and clinic factors. Significant variation in PCP adoption of CTC exists. PCP perceptions of CTC and specialty practice were related to CTC adoption. Strategies to increase PCP adoption of CTC for CRC screening should include emphasis on the effectiveness and advantages of CTC.

Background: Air emissions from concentrated animal feeding operations (CAFO) have been associated with respiratory and allergic symptoms among farm workers, primarily on swine farms. Despite the increasing prevalence of CAFOs, few studies have assessed respiratory health implications among residents living near CAFOs and few have looked at the health impacts of dairy CAFOs. Objectives: The goal of this study was to examine objective and subjective measures of respiratory and allergic health among rural residents living near dairy CAFOs in a general population living in the Upper Midwest of the United States. Methods: Data were from the 2008–2016 Survey of the Health of Wisconsin (SHOW) cohort (n = 5338), a representative, population based sample of rural adults (age 18+). The association between distance to the nearest CAFO and the prevalence of self-reported physician-diagnosed allergies, asthma, episodes of asthma in the last 12 months, and asthma medication use was examined using logistic regression, adjusting for covariates and sampling design. Similarly, the association between distance to the nearest CAFO and lung function, measured using spirometry, was examined using multivariate linear regression. Restricted cubic splines accounted for nonlinear relationships between distance to the nearest CAFO and the aforementioned outcomes. Results: Living 1.5 miles from a CAFO was associated with increased odds of self-reported nasal allergies (OR = 2.08; 95% CI: 1.38, 3.14), lung allergies (OR = 2.72; 95% CI: 1.59, 4.66), asthma (OR = 2.67; 95% CI: 1.39, 5.13), asthma medication (OR = 3.31; 95% CI: 1.65 6.62), and uncontrolled asthma, reported as an asthma episode in last 12 months (OR = 2.34; 95% CI: 1.11, 4.92) when compared to living 5 miles from a CAFO. Predicted FEV1 was 7.72% (95% CI: −14.63, −0.81) lower at a residential distance 1.5 miles from a CAFO when compared with a residence distance of 3 miles from a CAFO. Conclusions: Results suggest CAFOs may be an important source of adverse air quality associated with reduced respiratory and allergic health among rural residents living in close proximity to a CAFO. Keywords: Air pollution, Concentrated animal feeding operation, Lung function, Allergies, Asthma

IntroductionApproximately 25%–35% of the 1991 Gulf War Veteran population report symptoms consistent with Gulf War Illness (GWI), a chronic, multi-symptom illness characterised by fatigue, pain, irritable bowel syndrome and problems with cognitive function. GWI is a disabling problem for Gulf War Veterans, and there remains a critical need to identify innovative, novel therapies.Gut microbiota perturbation plays a key role in the symptomatology of other chronic multi-symptom illnesses, including myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). Given similarities between ME/CFS and GWI and the presence of gastrointestinal disorders in GWI patients, Veterans with GWI may also have gut abnormalities like those seen with ME/CFS. In this longitudinal cohort study, we are comparing the diversity (structure) and the metagenomes (function) of the gut microbiome between Gulf War Veterans with and without GWI. If we find differences in Veterans with GWI, the microbiome could be a target for therapeutic intervention to alleviate GWI symptoms.Methods and analysisParticipants answer questions about diet, exercise and lifestyle factors. Participants also complete a questionnaire (based on the Kansas case definition of GWI) regarding their medical history and symptoms; we use this questionnaire to group participants into GWI versus healthy control cohorts. We plan to enrol 52 deployed Gulf War Veterans: 26 with GWI and 26 healthy controls. Participants provide stool and saliva samples weekly for an 8-week period for microbiome analyses. Participants also provide blood samples at the beginning and end of this period, which we will use to compare measures of inflammation markers between the groups.Ethics and disseminationThe protocol was approved by the University of Wisconsin-Madison Health Sciences Institutional Review Board and the William S. Middleton Memorial Veterans Hospital Research and Development Committee. Results of this study will be submitted for publication in a peer-reviewed journal.

Epidemiologic and cross-sectional studies suggest that early life farming and animal exposures are associated with major health benefits, influencing immune development and modifying the subsequent risk of allergic diseases, including asthma. The Wisconsin Infant Study Cohort (WISC) study was established in central Wisconsin to test the hypothesis that early life animal farm exposures are associated with distinct innate immune cell maturation trajectories, decreased allergen sensitization and reduced respiratory viral illness burden during the first 2 years of life. Beginning in 2013, a total of 240 families have been enrolled, 16,522 biospecimens have been collected, and 4098 questionnaires have been administered and entered into a secure database. Study endpoints include nasal respiratory virus identification and respiratory illness burden score, allergic sensitization, expression of allergic disease, and anti-viral immune response maturation and profiles. The WISC study prospective design, broad biospecimen collections, and unique US rural community will provide insights into the role of environmental exposures on early life immune maturation profiles associated with protection from allergic sensitization and significant respiratory viral disease burden. The WISC study findings will ultimately inform development of new strategies to promote resistance to severe respiratory viral illnesses and design primary prevention approaches for allergic diseases for all infants. Electronic supplementary material The online version of this article (10.1186/s13104-019-4448-0) contains supplementary material, which is available to authorized users.

Background Chlorhexidine gluconate (CHG) bathing of hospitalized patients may have benefit in reducing hospital-acquired bloodstream infections (HABSIs). However, the magnitude of effect, implementation fidelity, and patient-centered outcomes are unclear. In this meta-analysis, we examined the effect of CHG bathing on prevention of HABSIs and assessed fidelity to implementation of this behavioral intervention. Methods We undertook a meta-analysis by searching Medline, EMBASE, CINAHL, Scopus, and Cochrane’s CENTRAL registry from database inception through January 4, 2019 without language restrictions. We included randomized controlled trials, cluster randomized trials and quasi-experimental studies that evaluated the effect of CHG bathing versus a non-CHG comparator for prevention of HABSIs in any adult healthcare setting. Studies of pediatric patients, of pre-surgical CHG use, or without a non-CHG comparison arm were excluded. Outcomes of this study were HABSIs, patient-centered outcomes, such as patient comfort during the bath, and implementation fidelity assessed through five elements: adherence, exposure or dose, quality of the delivery, participant responsiveness, and program differentiation. Three authors independently extracted data and assessed study quality; a random-effects model was used. Results We included 26 studies with 861,546 patient-days and 5259 HABSIs. CHG bathing markedly reduced the risk of HABSIs (IRR = 0.59, 95% confidence interval [CI]: 0.52–0.68). The effect of CHG bathing was consistent within subgroups: randomized (0.67, 95% CI: 0.53–0.85) vs. non-randomized studies (0.54, 95% CI: 0.44–0.65), bundled (0.66, 95% CI: 0.62–0.70) vs. non-bundled interventions (0.51, 95% CI: 0.39–0.68), CHG impregnated wipes (0.63, 95% CI: 0.55–0.73) vs. CHG solution (0.41, 95% CI: 0.26–0.64), and intensive care unit (ICU) (0.58, 95% CI: 0.49–0.68) vs. non-ICU settings (0.56, 95% CI: 0.38–0.83). Only three studies reported all five measures of fidelity, and ten studies did not report any patient-centered outcomes. Conclusions Patient bathing with CHG significantly reduced the incidence of HABSIs in both ICU and non-ICU settings. Many studies did not report fidelity to the intervention or patient-centered outcomes. For sustainability and replicability essential for effective implementation, fidelity assessment that goes beyond whether a patient received an intervention or not should be standard practice particularly for complex behavioral interventions such as CHG bathing. Trial registration Study registration with PROSPERO CRD42015032523. Electronic supplementary material The online version of this article (10.1186/s12879-019-4002-7) contains supplementary material, which is available to authorized users.

BackgroundActivity trackers are now ubiquitous in certain populations, with potential applications for health promotion and monitoring and chronic disease management. Understanding the accuracy of this technology is critical to the appropriate and productive use of wearables in health research. Although other peer-reviewed validations have examined other features (eg, steps and heart rate), no published studies to date have addressed the accuracy of automatic activity type detection and duration accuracy in wearable trackers. ObjectiveThe aim of this study was to examine the ability of 4 commercially available wearable activity trackers (Fitbits Flex 2, Fitbit Alta HR, Fitbit Charge 2, and Garmin Vívosmart HR), in a controlled setting, to correctly and automatically identify the type and duration of the physical activity being performed. MethodsA total of 8 activity types, including walking and running (on both a treadmill and outdoors), a run embedded in walking bouts, elliptical use, outdoor biking, and pool lap swimming, were tested by 28 to 34 healthy adult participants (69 total participants who participated in some to all activity types). Actual activity type and duration were recorded by study personnel and compared with tracker data using descriptive statistics and mean absolute percent error (MAPE). ResultsThe proportion of trials in which the activity type was correctly identified was 93% to 97% (depending on the tracker) for treadmill walking, 93% to 100% for treadmill running, 36% to 62% for treadmill running when preceded and followed by a walk, 97% to 100% for outdoor walking, 100% for outdoor running, 3% to 97% for using an elliptical, 44% to 97% for biking, and 87.5% for swimming. When activities were correctly identified, the MAPE of the detected duration versus the actual activity duration was between 7% and 7.9% for treadmill walking, 8.7% and 144.8% for treadmill running, 23.6% and 28.9% for treadmill running when preceded and followed by a walk, 4.9% and 11.8% for outdoor walking, 5.6% and 9.6% for outdoor running, 9.7% and 13% for using an elliptical, 9.5% and 17.7% for biking, and was 26.9% for swimming. ConclusionsIn a controlled setting, wearable activity trackers provide accurate recognition of the type of some common physical activities, especially outdoor walking and running and walking on a treadmill. The accuracy of measurement of activity duration varied considerably by activity type and tracker model and was poor for complex sets of activity, such as a run embedded within 2 walking segments.

Antiretroviral therapy is successfully administered to people living with HIV while they are incarcerated in most U.S. prison systems, but interruptions in treatment are common after people are released. We undertook an observational cohort study designed to examine the clinical and psychosocial factors that influence linkage to HIV care and viral suppression after release from a single state prison system. In this report we describe baseline characteristics and 6-month post-incarceration HIV care outcomes for 170 individuals in Wisconsin. Overall, 114 (67%) individuals were linked to outpatient HIV care within 180 days of release from prison, and of these, 90 (79%) were observed to have HIV viral suppression when evaluated in the community. The strongest predictor of linkage to care in this study was participation in a patient navigation program: Those who received patient navigation were linked to care 84% of the time, compared to 60% of the individuals who received only standard release planning (adjusted OR=3.69, 95% CI: 1.24, 10.96; P

Season is a major determinant of infectious disease rates, including arboviruses spread by mosquitoes, such as dengue, chikungunya, and Zika. Seasonal patterns of disease are driven by a combination of climatic or environmental factors, such as temperature or rainfall, and human behavioral time trends, such as school year schedules, holidays, and weekday-weekend patterns. These factors affect both disease rates and healthcare-seeking behavior. Seasonality of dengue fever has been studied in the context of climatic factors, but short- and long-term time trends are less well-understood. With 2009—2016 medical record data from patients diagnosed with dengue fever at two hospitals in rural Ecuador, we used Poisson generalized linear modeling to determine short- and long-term seasonal patterns of dengue fever, as well as the effect of day of the week and public holidays. In a subset analysis, we determined the impact of school schedules on school-aged children. With a separate model, we examined the effect of climate on diagnosis patterns. In the first model, the most important predictors of dengue fever were annual sinusoidal fluctuations in disease, long-term trends (as represented by a spline for the full study duration), day of the week, and hospital. Seasonal trends showed single peaks in case diagnoses, during mid-March. Compared to the average of all days, cases were more likely to be diagnosed on Tuesdays (risk ratio (RR): 1.26, 95% confidence interval (CI) 1.05—1.51) and Thursdays (RR: 1.25, 95% CI 1.02—1.53), and less likely to be diagnosed on Saturdays (RR: 0.81, 95% CI 0.65—1.01) and Sundays (RR: 0.74, 95% CI 0.58—0.95). Public holidays were not significant predictors of dengue fever diagnoses, except for an increase in diagnoses on the day after Christmas (RR: 2.77, 95% CI 1.46—5.24). School schedules did not impact dengue diagnoses in school-aged children. In the climate model, important climate variables included the monthly total precipitation, an interaction between total precipitation and monthly absolute minimum temperature, an interaction between total precipitation and monthly precipitation days, and a three-way interaction between minimum temperature, total precipitation, and precipitation days. This is the first report of long-term dengue fever seasonality in Ecuador, one of few reports from rural patients, and one of very few studies utilizing daily disease reports. These results can inform local disease prevention efforts, public health planning, as well as global and regional models of dengue fever trends.Author summaryDengue fever exhibits a seasonal pattern in many parts of the world, much of which has been attributed to climate and weather. However, additional factors may contribute to dengue seasonality. With 2009— 2016 medical record data from rural Ecuador, we studied the short- and long-term seasonal patterns of dengue fever, as well as the effect of school schedules and public holidays. We also examined the effect of climate on dengue. We found that dengue diagnoses peak once per year in mid-March, but that diagnoses are also affected by day of the week. Dengue was also impacted by regional climate and complex interactions between local weather variables. This is the first report of long-term dengue fever seasonality in Ecuador, one of few reports from rural patients, and one of very few studies utilizing daily disease reports. This is the first report on the impacts of school schedules, holidays, and weekday-weekend patterns on dengue diagnoses. These results suggest a potential impact of human behaviors on dengue exposure risk. More broadly, these results can inform local disease prevention efforts and public health planning, as well as global and regional models of dengue fever trends.

Background Farm exposures may reduce the risk of atopic dermatitis (AD) in children, but this is controversial and US data are limited. Objective This study was conducted to identify patterns of farm exposure in Wisconsin family farms that modify AD incidence and prevalence in early childhood. Methods Environmental exposures, health history, and clinical outcomes were prospectively recorded for 111 farm families and 129 non–farm families enrolled in the Wisconsin Infant Study Cohort birth cohort study. Exposures from the prenatal and early postnatal (2-month) visits were evaluated together with parental report of AD diagnosis by a health care provider through age 24 months. Latent class analysis was performed with prenatal and early postnatal farm-exposure variables to assign farm children to 3 classes. Results Overall, children of farm families had reduced AD incidence (P = .03). Within farm families, exposures including poultry (3% vs 28%; P = .003), pig (4% vs 25%; P = .04), feed grain (13% vs 34%; P = .02), and number of animal species were inversely associated with AD incidence. Among the latent class groups, children in families with diverse or more intense farm exposures (classes A and B) had reduced AD incidence, whereas low-exposure (class C) infants had AD incidence similar to that in nonfarm children. Conclusions Infants in Wisconsin farm families had reduced AD incidence, and patterns of farm exposures further defined AD risk. These findings suggest that exposure to diverse farm animals, feed, and bedding during the prenatal period and in early infancy reduce the risk of early-onset AD, a phenotype associated with multiple other atopic diseases.

Background The use of surgery and radiation therapy in treating ductal carcinoma in situ (DCIS) is directed by treatment guidelines and evidence from research. This study investigated recent patterns in DCIS treatment by demographic factors. Methods Data for women diagnosed with DCIS between 1998 and 2011 (n = 416,232) in the National Cancer Data Base were assessed for trends in treatment patterns by age group, calendar year, ancestral/ethnic group, and geographic region. The likelihood of receiving specific treatment modalities was analyzed with multivariable logistic regression. Results DCIS cases were most frequently treated with breast-conserving surgery (BCS) and adjuvant radiation (45.6%). After an initial rise, the use of adjuvant radiation after BCS plateaued at approximately 70% after 2007, with increasing utilization of mastectomy beyond 2005. In addition, there was an increasing trend in postmastectomy reconstruction over time, and women of African ancestry (odds ratio [OR], 0.69; 95% confidence interval [CI], 0.66-0.72) and Hispanic women (OR, 0.83; 95% CI, 0.78-0.89) were less likely to undergo reconstruction in comparison with women of European ancestry. A similar trend was observed in contralateral risk-reducing mastectomy utilization, with women of European ancestry having a more rapid rise in the utilization of contralateral risk-reducing mastectomy in comparison with all other ancestral/ethnic groups. Conclusions Recent trends demonstrate a plateau in radiation therapy administration after BCS along with increasing utilization of mastectomy, reconstruction, and contralateral risk-reducing mastectomy. There are substantial differences in treatment utilization according to ancestry/ethnicity and geographical region. Further studies examining patient-physician decision making surrounding DCIS treatment are warranted. Cancer 2016. © 2016 American Cancer Society. Cancer 2016;122:2810-2818. © 2016 American Cancer Society.

We hypothesized that persons with type 1 diabetes with higher serum levels of carboxymethyl lysine (CML) and soluble receptor for advanced glycation end products (sRAGE) are at a higher risk of developing incident diabetic nephropathy (DN). We examined this hypothesis using data from up to four follow-up examinations over a 22-year period in persons with type 1 diabetes participating in the Wisconsin Epidemiologic Study of Diabetic Retinopathy (WESDR). We also examined the relationship of CML and sRAGE to mortality. Descriptions of the cohort, participation statistics, and reasons for nonparticipation have appeared elsewhere (1). Of 1,210 persons with type 1 diabetes receiving care in an 11-county area of south central Wisconsin in 1979–1980, 996 were examined in 1980–1982. The individuals were 3–79 years of age with type 1 diabetes duration of 1–59 years. These persons participated in up to six follow-up examinations in 1984–1986 ( n = 903), 1990–1992 ( n = 816), 1994–1996 ( n = 667), 2000–2001 ( n = 567), 2005–2007 ( n = 520), and 2012–2014 ( n = 414). The tenets of the Declaration of Helsinki were followed, and institutional review board approval was obtained from the University of Wisconsin–Madison. Written informed consent was obtained. Starting with the third examination in 1990–1992 and continuing with follow-up examinations, serum was collected, processed, and frozen at −80°C. Serum sRAGE and CML levels were measured …

Surveillance reports consistently observe that cancer mortality rates are higher in rural than urban areas, yet data on the multi-level factors that impact rural disparities have not been fully leveraged to identify the areas of greatest need for research and policy changes. To address gaps in cancer data for rural communities, we adapted the County Health Rankings model of the multiple determinants of health to cancer. Using publicly available data, we compared health factors and cancer mortality for rural versus urban counties in Wisconsin. Counties were defined as rural (N=19) or non-rural (“urban”, N=53) based on Rural Urban Continuum Codes 7-9 and 1-6, respectively. Age-adjusted county-specific cancer mortality rates for all cancer sites combined were obtained from the state cancer registry. Health factor data were obtained from multiple sources in 4 categories: health behaviors (smoking, drinking alcohol, obesity, physical activity); clinical care (HPV vaccination; breast, cervical, and colorectal cancer screening; density of primary care physicians); socioeconomic factors (Area Deprivation Index based on 17 census items); and physical environment (access to grocery stores and alcohol outlets, air quality, pesticide use). Items were ranked for the 72 counties with lower-risk values having better ranks, e.g., higher values for screening and lower values for obesity ranked closer to 1. A composite health factor ranking was defined using County Health Rankings weights, equal to 0.3*(behavioral factors) + 0.2*(clinical factors) + 0.4*(socioeconomic factors) + 0.1*(physical environment). Cancer death rates were higher in rural than in urban counties (181 vs 164 per 100,000). The composite health ranking was positively associated with cancer mortality rates (Pearson correlation coefficient 0.38, 95% CI 0.17-0.57), with worse rankings for rural (average 44, interquartile range, IQR 39-51) than for urban counties (average 34, IQR 25-42). The difference in health factor category rankings between rural and urban counties was greatest for socioeconomic factors (rural average rank 50 vs urban average rank 32) followed by clinical care (rural average rank 43 vs urban average rank 34) and behavioral factors (rural average rank 40 vs urban average rank 35). Physical environment factor rankings were slightly better for rural (average 33) than urban (average 37) counties. In conclusion, we confirmed that cancer mortality in Wisconsin is higher in rural as compared with urban areas. Future analyses will (a) refine the set of health factors used to construct the composite health factor ranking (e.g., account more fully for distance to care) and (b) optimize the weights applied to the categories to calculate the composite ranking. These initial findings suggest that, to increase the impact of future research and policy efforts, clinical and behavioral interventions targeting cancer health disparities in rural counties should include strategies to address socioeconomic factors. Citation Format: Amy Trentham-Dietz, Noelle K LoConte, Betsy Rolland, Lisa Cadmus-Bertram, Tracy M Downs, John M Eason, Cody M Fredrick, John M Hampton, Xiao Zhang, Ronald E Gangnon. Associations between multilevel health factors and cancer mortality according to rural residence [abstract]. In: Proceedings of the Twelfth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2019 Sep 20-23; San Francisco, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(6 Suppl_2):Abstract nr D002.

Background: For breast cancer, black women experience younger mean age at diagnosis, higher incidence of triple negative disease, and higher mortality compared to the overall population. These epidemiological differences raise the question of whether different screening mammography schedules for black women might produce similar benefit-to-harm ratio as those currently recommended for the overall population. Methods: We used the Georgetown-Einstein Cancer Intervention and Surveillance Modeling Network (CISNET) model to compare the benefit-to-harm ratios of a variety of digital mammography screening schedules for black women and white women. We updated the models with a variety of race-specific inputs, including non-breast cancer (competing) mortality, breast density, mammography sensitivity, breast cancer incidence with and without screening, estrogen (ER) and Her-2 receptor distributions, and stage distributions. Within age, stage, and ER/Her-2 receptor strata, we assumed that breast cancer biology was the same across races, as reflected by equal sojourn, stage dwell time and treatment efficacy. The objective of this study was to isolate the impact of screening mammography, not to quantify the impact of differences in screening or treatment completion on disparities. Therefore, in keeping with previously published methods, we assumed 100% dissemination of screening mammography and adjuvant treatment for all races. We investigated annual, biennial, and hybrid screening strategies beginning at age 40, 45, or 50 and concluding at age 74 (e.g. “A40-B50-74” means annually starting at age 40, then biennially at age 50, then stopping at age 74). We quantified the number of mammograms (M), overdiagnoses, false positives (FP), breast cancer deaths averted (BCDA), life years gained (LYG) and their benefit-to-harm ratios (LYG:M, BCDA:M, LYG:FP, BCDA:FP). Results: Biennial strategies (B50-74, B45-74, B40-74) have approximately equal incremental benefit:harm ratios and are superior to annual or hybrid strategies. Hybrid strategies A40B50-74 and B40A50-74 are sometimes efficient, depending on the metric, but have lower incremental benefit:harm ratios than the biennial strategies. Results were similar for black and white women. Conclusions: Despite the fact that black women have a younger mean age at diagnosis, higher incidence of triple negative disease, and higher breast cancer mortality, the relative benefits of different screening mammography schedules do not appear to differ between black and white women. These findings do not support different screening guidelines for black and white women. Future analyses will investigate whether potential racial differences in treatment efficacy might change the relative benefits of different screening mammography schedules. Citation Format: Christina H Chapman, Clyde Schechter, Amy Trentham, Ron Gangnon, Chris Cadham, Jeanne Mandelblatt. Would black women benefit from a screening mammography schedule that differs from that recommended for the overall population? A simulation modeling study [abstract]. In: Proceedings of the Twelfth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2019 Sep 20-23; San Francisco, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(6 Suppl_2):Abstract nr A005.

Background and objectives Falls among older adults is a pressing public health challenge. Considerable research documents that longer tai chi courses can reduce falls and improve balance. However, longer courses can be challenging to implement. Our goal was to evaluate whether a short 6-week modified tai chi course could be effective at reducing falls risk if older adults designed a personal home practice plan to receive a greater tai chi "dose" during the 6 weeks. Design A 3-city wait-listed randomized trial was conducted. Habituation Intention and Social Cognitive Theories framed the "coaching" strategy by which participants designed practice plans. RE-AIM and Treatment Fidelity Frameworks were used to evaluate implementation and dissemination issues. Three advisory groups advised the study on intervention planning, implementation, and evaluation. To measure effectiveness, we used Centers for Disease Control and Prevention recommended measures for falls risk including leg strength, balance, and mobility and gait. In addition, we measured balance confidence and executive function. Results Program Implementation resulted in large class sizes, strong participant retention, high program fidelity and effectiveness. Participants reported practicing an average of 6 days a week and more than 25 min/day. Leg strength, tandem balance, mobility and gait, balance confidence, and executive function were significantly better for the experimental group than control group. Conclusion The tai chi short course resulted in substantial tai chi practice by older adults outside of class as well as better physical and executive function. The course reach, retention, fidelity, and implementation across 3 cities suggest strong potential for implementation and dissemination of the 6-week course.

Purpose To examine the relationship between serum oxidized low-density lipoprotein (ox-LDL) cholesterol and the incidence of age-related macular degeneration (AMD) over a 25-year period in a sample of persons from the population-based Beaver Dam Eye Study (BDES). Design Observational prospective cohort study. Participants A total of 4972 people from the BDES (aged 43–84 years and living in Beaver Dam, Wisconsin in 1988) seen during at least 1 of 6 examination phases at approximately 5-year intervals between 1988 and 2016. Methods A 50% random sample of participants (N = 2468) was selected for ox-LDL measurements. Stored frozen specimens from every examination phase were processed using an enzyme-linked immunosorbent assay from a single batch. All available intervals were included for a person, resulting in 6586 person-visits. Main Outcome Measures Age-related macular degeneration was assessed using the Wisconsin Age-related Maculopathy Grading System, and severity was defined using a 5-step severity scale. The severity of the worse eye at each examination was used for analyses. A multi-state Markov (MSM) model was fit to simultaneously assess the ox-LDL relationship to all AMD transitions, including incidence of any AMD, incidence of late AMD, and worsening and improvement of AMD over the 25 years of the study. Results The mean (standard deviation) level of ox-LDL was 75.3 (23.1) U/L at the baseline examination. When adjusting for age, sex, ARMS2 and CFH risk alleles, and examination phase, the ox-LDL at the beginning of a period was not statistically significantly associated with the incidence of any AMD (hazard ratio per 10 U/L ox-LDL was 1.03, 95% confidence interval 0.98,1.09). Furthermore, ox-LDL was not associated with worsening anywhere along the AMD severity scale, nor with incidence of late AMD. The lack of relationships of ox-LDL to the incidence of any AMD or worsening of AMD remained after adjustment for history of statin use, smoking status, body mass index, and history of cardiovascular disease (data not shown). Conclusions Our findings do not provide evidence for statistically significant relationships between ox-LDL and AMD disease development or worsening of AMD.

PURPOSE: Heavy metals and other elements may act as breast carcinogens due to estrogenic activity. We investigated associations between urine concentrations of a panel of elements and breast density. METHODS: Mammographic density categories were abstracted from radiology reports of 725 women aged 40–65 years in the Avon Army of Women. A panel of 27 elements was quantified in urine using high resolution magnetic sector inductively coupled plasma mass spectroscopy. We applied LASSO (least absolute shrinkage and selection operator) logistic regression to the 27 elements and calculated odds ratios (OR) and 95% confidence intervals (CI) for dense versus non-dense breasts, adjusting for potential confounders. RESULTS: Of the 27 elements, only magnesium (Mg) was selected into the optimal regression model. The odds ratio for dense breasts associated with doubling the Mg concentration was 1.24 (95% CI 1.03–1.49). Doubling the calcium-to-magnesium ratio was inversely associated with dense breasts (OR 0.83, 95% CI 0.70–0.98). CONCLUSIONS: Our cross-sectional study found that higher levels of urinary magnesium were associated with greater breast density. Prospective studies are needed to confirm whether magnesium as evaluated in urine is prospectively associated with breast density and, more importantly, breast cancer.

PURPOSE. Women diagnosed with ductal carcinoma in situ (DCIS) often experience adverse changes in health-related behaviors following diagnosis. The impact of health behaviors on long-term quality of life (QoL) in DCIS survivors has not been investigated. METHODS. We examined the association of post-diagnosis body mass index (BMI), physical activity, alcohol, and smoking with QoL among 1,448 DCIS survivors aged 20–74 enrolled in the population-based Wisconsin in Situ Cohort from 1997–2006. Health behaviors and QoL were self-reported during biennial post-diagnosis interviews. Physical and mental QoL were measured using the validated SF-36 questionnaire. Generalized linear regression was used to determine the association between behaviors and QoL with adjustment for confounders. Lagged behavior variables were used to predict QoL during follow-up and avoid reverse causation. RESULTS. Women reported 3,536 QoL observations over an average 7.9 years of follow-up. Women maintaining a healthy BMI had on average a significantly higher summary measure score of physical QoL than obese women (normal vs. obese: β = 3.02; 2.18, 3.85). Physical QoL scores were also elevated among those who were physically active (5+ hours/week vs. none: β = 1.96; 0.72, 3.20), those consuming at least 7 drinks/week of alcohol (vs. none; β = 1.40; 0.39, 2.41), and non-smokers (vs. current smokers: β = 1.80; 0.89, 2.71). Summary measures of mental QoL were significantly higher among women who were moderately physically active (up to 2 hours/week vs. none: β = 1.11; 0.30, 1.92) and non-smokers (vs. current smokers: β = 1.49;0.45, 2.53). CONCLUSIONS. Our results demonstrate that maintaining healthy behaviors following DCIS treatment is associated with modest improvements in long-term QoL. These results inform interventions aimed at promoting healthy behaviors and optimizing QoL in DCIS survivors.

Importance Given recent advances in screening mammography and adjuvant therapy (treatment), quantifying their separate and combined effects on US breast cancer mortality reductions by molecular subtype could guide future decisions to reduce disease burden. Objective To evaluate the contributions associated with screening and treatment to breast cancer mortality reductions by molecular subtype based on estrogen-receptor (ER) and human epidermal growth factor receptor 2 ( ERBB2 , formerly HER2 or HER2/neu ). Design, Setting, and Participants Six Cancer Intervention and Surveillance Network (CISNET) models simulated US breast cancer mortality from 2000 to 2012 using national data on plain-film and digital mammography patterns and performance, dissemination and efficacy of ER /ERBB2 -specific treatment, and competing mortality. Multiple US birth cohorts were simulated. Exposures Screening mammography and treatment. Main Outcomes and Measures The models compared age-adjusted, overall, and ER /ERBB2 -specific breast cancer mortality rates from 2000 to 2012 for women aged 30 to 79 years relative to the estimated mortality rate in the absence of screening and treatment (baseline rate); mortality reductions were apportioned to screening and treatment. Results In 2000, the estimated reduction in overall breast cancer mortality rate was 37% (model range, 27%-42%) relative to the estimated baseline rate in 2000 of 64 deaths (model range, 56-73) per 100 000 women: 44% (model range, 35%-60%) of this reduction was associated with screening and 56% (model range, 40%-65%) with treatment. In 2012, the estimated reduction in overall breast cancer mortality rate was 49% (model range, 39%-58%) relative to the estimated baseline rate in 2012 of 63 deaths (model range, 54-73) per 100 000 women: 37% (model range, 26%-51%) of this reduction was associated with screening and 63% (model range, 49%-74%) with treatment. Of the 63% associated with treatment, 31% (model range, 22%-37%) was associated with chemotherapy, 27% (model range, 18%-36%) with hormone therapy, and 4% (model range, 1%-6%) with trastuzumab. The estimated relative contributions associated with screening vs treatment varied by molecular subtype: for ER +/ERBB2− , 36% (model range, 24%-50%) vs 64% (model range, 50%-76%); for ER+ /ERBB2+ , 31% (model range, 23%-41%) vs 69% (model range, 59%-77%); for ER− /ERBB2+ , 40% (model range, 34%-47%) vs 60% (model range, 53%-66%); and for ER− /ERBB2− , 48% (model range, 38%-57%) vs 52% (model range, 44%-62%). Conclusions and Relevance In this simulation modeling study that projected trends in breast cancer mortality rates among US women, decreases in overall breast cancer mortality from 2000 to 2012 were associated with advances in screening and in adjuvant therapy, although the associations varied by breast cancer molecular subtype.

Purpose To assess the association between geographic access to mammography facilities and women's mammography utilization frequency. Methods Using data from the population-based 1995–2007 Wisconsin Women's Health study, we used proportional odds and logistic regression to test whether driving times to mammography facilities and the number of mammography facilities within 10 km of women's homes were associated with mammography frequency among women aged 50–74 years and whether associations differed between Rural-Urban Commuting Areas and income and education groups. Results We found evidence for nonlinear relationships between geographic access and mammography utilization (nonlinear effects of driving times and facility density, P -values .01 and .005, respectively). Having at least one nearby mammography facility was associated with greater mammography frequency among urban women (1 vs. 0 facilities, odds ratio 1.26, 95% confidence interval, 1.09–1.47), with similar effects among rural women. Adding more facilities had decreasing marginal effects. Long driving times tended to be associated with lower mammography frequency. We found no effect modification by income, education, or urbanicity. In rural settings, mammography nonuse was higher, facility density smaller, and driving times to facilities were longer. Conclusions Having at least one mammography facility near one's home may increase mammography utilization, with decreasing effects per each additional facility.

Background Sex influences the risk of wheezing illnesses and the prevalence of asthma throughout childhood. Objective To better understand the mechanisms of these effects, we analyzed longitudinal relationships between sex, lung physiology, and asthma in the Childhood Origins of ASThma birth cohort study. Methods Childhood Origins of ASThma birth cohort study children were followed prospectively from birth and assessed annually. Results of spirometry, fractional exhaled nitric oxide (Feno), mannitol provocation testing, and 3 He gas magnetic resonance imaging were assessed by sex using multivariate models including age, asthma diagnosis, and wheezing histories. Results Girls had higher prebronchodilator forced expiratory volume in 0.5 seconds/forced vital capacity values than did boys (mean difference, 0.017; 95% CI, 0.000-0.034; P = .05) of equivalent age. Postbronchodilator findings were more pronounced, with boys demonstrating reduced forced expiratory volume in 0.5 seconds/forced vital capacity values than did girls of equivalent age (mean difference, 0.032; 95% CI, 0.014-0.049; P = .0005). Conversely, girls were noted to have higher ventilation defects on 3 He magnetic resonance imaging than did boys ( P = .01). No differences were noted in the rate of positive responses to mannitol provocation or Feno measurements. Conclusions Lower airflow values are present by spirometry for prepubertal boys than for age-matched girls; however, greater 3 He ventilation defects were noted in girls. This could represent a greater degree of subclinical air trapping in prepubertal girls because residual volumes are not detected on standard spirometric readings. No differences were noted between the 2 sexes with airway hyperresponsiveness (mannitol provocation testing) or inflammation (Feno). Prospective peripubertal follow-up will determine whether these differences persist or change with the de novo expression and remission of asthma based on sex and age.

Concerns about breast cancer overdiagnosis have increased the need to understand how cancers detected through screening mammography differ from those first detected by a woman or her clinician. We investigated risk factor associations for invasive breast cancer by method of detection within a series of case-control studies (1992–2007) carried out in Wisconsin, Massachusetts, and New Hampshire (n = 15,648 invasive breast cancer patients and 17,602 controls aged 40–79 years). Approximately half of case women reported that their cancer had been detected by mammographic screening and half that they or their clinician had detected it. In polytomous logistic regression models, parity and age at first birth were more strongly associated with risk of mammography-detected breast cancer than with risk of woman/clinician-detected breast cancer (P ≤ 0.01; adjusted for mammography utilization). Among postmenopausal women, estrogen-progestin hormone use was predominantly associated with risk of woman/clinician-detected breast cancer (odds ratio (OR) = 1.49, 95% confidence interval (CI): 1.29, 1.72), whereas obesity was predominantly associated with risk of mammography-detected breast cancer (OR = 1.72, 95% CI: 1.54, 1.92). Among regularly screened premenopausal women, obesity was not associated with increased risk of mammography-detected breast cancer (OR = 0.99, 95% CI: 0.83, 1.18), but it was associated with reduced risk of woman/clinician-detected breast cancer (OR = 0.53, 95% CI: 0.43, 0.64). These findings indicate important differences in breast cancer risk factors according to method of detection.

We tested the hypothesis that large areas of small hard drusen (diameter &lt, 63 µm) and intermediate drusen (diameter 63–124 µm) are associated with the incidence of age-related macular degeneration (AMD). Eyes of 3344 older adults with at least two consecutive visits spaced five years apart over a 20-year period were included. A 6-level severity scale, including no drusen, four levels of increasing area (from minimal (&lt, 2596 µm²) to large (&gt, 9086 µm²)) of only small hard drusen, and intermediate drusen, was used. The five-year incidence of AMD was 3% in eyes at the start of the interval with no, minimal, small, and moderate areas of only small drusen and 5% and 25% for eyes with large area of only small drusen and intermediate drusen, respectively. Compared to eyes with a moderate area of small drusen, the odds ratio (OR) of developing AMD in eyes with a large area of only small drusen was 1.8 (p &lt, 0.001). Compared to eyes with large area of only small drusen, eyes with intermediate drusen had an OR of 5.5 (p &lt, 0.001) of developing AMD. Our results are consistent with our hypothesis that large areas of only small drusen are associated with the incidence of AMD.

Given larger bone size in men, bone mineral density (BMD) precision might differ between sexes. This study compared dual-energy X-ray absorptiometry BMD precision of 3 International Society for Clinical Densitometry-certified technologists in older men and women. Each technologist scanned a cohort of 30 men and 30 women (total n = 180) by using a Lunar iDXA densitometer (GE Healthcare, Madison, WI). Each volunteer had 2 lumbar spine and bilateral hip scans with repositioning between examinations. BMD least significant change was calculated. Age and body mass index did not differ between men and women. Mean height and weight were greater in men, 174.6 cm ± 6.9 and 81.6 kg ± 11.1 respectively, (p0.0001) than in women, 161.5 cm ± 5.9/69.1 kg ± 14.2, respectively. Bone area was greater in men (p0.0001) at all sites. BMD least significant change was statistically better (p0.05) in women at the mean total femur (0.014 vs 0.018 g/cm(2)) and left femoral neck (0.025 vs 0.038 g/cm(2)), but not different at either total femur, the right femoral neck, or lumbar spine (all p0.05). In conclusion, statistically significant male/female differences in BMD precision were observed at the mean total femur and left femoral neck. Given the small magnitude of difference in g/cm(2) and inconsistent pattern, that is, no right femoral neck difference, there is virtually no clinical difference in BMD precision between sexes. These data do not support a need for sex-specific precision analyses.

Purpose To compare overall colorectal cancer (CRC) screening rates for patients who were eligible and due for CRC screening and who were with and without insurance coverage for computed tomographic (CT) colonography for CRC screening. Materials and Methods The institutional review board approved this retrospective cohort study, with a waiver of consent. This study used longitudinal electronic health record data from 2005 through 2010 for patients managed by one of the largest multispecialty physician groups in the United States. It included 33 177 patients under age 65 who were eligible and due for CRC screening and managed by the participating health system. Stratified Cox regression models provided propensity-adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for the relationship between CT colonography coverage and CRC screening. Results After adjustment, patients who had insurance coverage for CT colonography and were due for CRC screening had a 48% greater likelihood of being screened for CRC by any method compared with those without coverage who were due for CRC screening (HR, 1.48; 95% CI: 1.41, 1.55). Similarly, patients with CT colonography coverage had a greater likelihood of being screened with CT colonography (HR, 8.35; 95% CI: 7.11, 9.82) and with colonoscopy (HR, 1.38; 95% CI: 1.31, 1.45) but not with fecal occult blood test (HR, 1.00; 95% CI: 0.91, 1.10) than those without such insurance coverage. Conclusion Insurance coverage of CT colonography for CRC screening was associated with a greater likelihood of a patient being screened and a greater likelihood of being screened with a test that helps both to detect cancer and prevent cancer from developing (CT colonography or colonoscopy).