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Background: Childhood cancer survivors experience reduced physiologic reserve, or frailty, earlier and more frequently than peers. In other populations, frailty is impacted by one's neighborhood. This study's purpose was to evaluate associations between neighborhood characteristics and frailty in childhood cancer survivors. Methods: Participants in the St. Jude Lifetime Cohort Study with geocoded residential addresses were analyzed. Pre-frailty/Frailty was defined as having 1–2/≥3 of sarcopenia, muscle weakness, poor endurance, slow walking speed, and exhaustion from direct assessments. Neighborhood characteristics [e.g., access to exercise opportunities and healthy food, neighborhood socioeconomic status (nSES), and rurality/urbanicity] were determined using publicly available geospatial data. Nested multivariable logistic regression models identified associations between neighborhood characteristics and pre-frailty/frailty, adjusting for chronic health conditions, individual health behaviors and socio-demographics, and high-risk cancer treatment exposures. Results: For our cohort (N = 3,806, 46.79% female, 81.40% white, mean age 33.63±9.91 years), compared with non-frail survivors (n = 2,573; 67.6%), pre-frail (n = 900; 23.6%) and frail survivors (n = 333; 8.7%) were more likely to live in neighborhoods with decreased exercise opportunities (frail OR: 1.62, 1.26–2.09), reduced healthy food access (pre-frail OR: 1.28, 1.08–1.51; frail OR: 1.36, 1.06–1.75), and lower nSES (pre-frail OR: 1.31, 1.12–1.52; frail OR: 1.64, 1.30–2.07). Participants had 8% increased odds (95% confidence interval, 2%–14%) of being pre-frail/frail if they lived in “resource poor” neighborhoods as opposed to “resource rich” neighborhoods after adjusting for other pre-frailty/frailty risk factors. Conclusions: The neighborhood a childhood cancer survivor resides in as an adult is associated with pre-frailty/frailty. Impact: This study provides valuable information for creating interventions using neighborhood-level factors to mitigate frailty and improve health outcomes in survivors.

Background:Childhood cancer survivors experience reduced physiologic reserve, or frailty, earlier and more frequently than peers. In other populations, frailty is impacted by one's neighborhood. This study's purpose was to evaluate associations between neighborhood characteristics and frailty in childhood cancer survivors.Methods:Participants in the St. Jude Lifetime Cohort Study with geocoded residential addresses were analyzed. Pre-frailty/Frailty was defined as having 1–2/≥3 of sarcopenia, muscle weakness, poor endurance, slow walking speed, and exhaustion from direct assessments. Neighborhood characteristics [e.g., access to exercise opportunities and healthy food, neighborhood socioeconomic status (nSES), and rurality/urbanicity] were determined using publicly available geospatial data. Nested multivariable logistic regression models identified associations between neighborhood characteristics and pre-frailty/frailty, adjusting for chronic health conditions, individual health behaviors and socio-demographics, and high-risk cancer treatment exposures.Results:For our cohort (N = 3,806, 46.79% female, 81.40% white, mean age 33.63±9.91 years), compared with non-frail survivors (n = 2,573; 67.6%), pre-frail (n = 900; 23.6%) and frail survivors (n = 333; 8.7%) were more likely to live in neighborhoods with decreased exercise opportunities (frail OR: 1.62, 1.26–2.09), reduced healthy food access (pre-frail OR: 1.28, 1.08–1.51; frail OR: 1.36, 1.06–1.75), and lower nSES (pre-frail OR: 1.31, 1.12–1.52; frail OR: 1.64, 1.30–2.07). Participants had 8% increased odds (95% confidence interval, 2%–14%) of being pre-frail/frail if they lived in “resource poor” neighborhoods as opposed to “resource rich” neighborhoods after adjusting for other pre-frailty/frailty risk factors.Conclusions:The neighborhood a childhood cancer survivor resides in as an adult is associated with pre-frailty/frailty.Impact:This study provides valuable information for creating interventions using neighborhood-level factors to mitigate frailty and improve health outcomes in survivors.

Supplementary Table S2 shows the results of bivariate analyses between individual-level participant variables and frailty status

Supplementary Figure S1: Geographic location of study participants (N=3806). In this map, each red dot indicates the address of each participant recorded at intake and geocoded for this study.

Employing an ecological approach, we sought to identify social determinants of obesity among Hispanics/Latinos and non-Hispanic whites living in the Southeast US. Data on social determinants of obesity (individual, family, community and cultural/contextual) were collected from 217 participants [106 Hispanics/Latinos; 111 non-Hispanic whites]; height and weight were objectively measured. We compared prevalence of overweight and obese between ethnic groups and BMI values within each group by social determinants. Hispanics had a 1.9-fold increase (OR 1.93, 95% CI: 1.05-3.55) in overweight prevalence compared to non-Hispanic whites after adjusting for age and gender. We found positive estimates between unfavorable family-level determinants and BMI among Hispanic/Latinos. In contrast, non-Hispanic whites who reported unfavorable neighborhood characteristics had higher BMI's. Findings highlight the need for targeted approaches for the prevention and control of obesity.

OBJECTIVE We examined whether relative availability of fast-food restaurants and supermarkets mediates the association between worse neighborhood socioeconomic conditions and risk of developing type 2 diabetes (T2D). RESEARCH DESIGN AND METHODS As part of the Diabetes Location, Environmental Attributes, and Disparities Network, three academic institutions used harmonized environmental data sources and analytic methods in three distinct study samples: 1) the Veterans Administration Diabetes Risk (VADR) cohort, a national administrative cohort of 4.1 million diabetes-free veterans developed using electronic health records (EHRs); 2) Reasons for Geographic and Racial Differences in Stroke (REGARDS), a longitudinal, epidemiologic cohort with Stroke Belt region oversampling (N = 11,208); and 3) Geisinger/Johns Hopkins University (G/JHU), an EHR-based, nested case-control study of 15,888 patients with new-onset T2D and of matched control participants in Pennsylvania. A census tract–level measure of neighborhood socioeconomic environment (NSEE) was developed as a community type-specific z-score sum. Baseline food-environment mediators included percentages of 1) fast-food restaurants and 2) food retail establishments that are supermarkets. Natural direct and indirect mediating effects were modeled; results were stratified across four community types: higher-density urban, lower-density urban, suburban/small town, and rural. RESULTS Across studies, worse NSEE was associated with higher T2D risk. In VADR, relative availability of fast-food restaurants and supermarkets was positively and negatively associated with T2D, respectively, whereas associations in REGARDS and G/JHU geographies were mixed. Mediation results suggested that little to none of the NSEE–diabetes associations were mediated through food-environment pathways. CONCLUSIONS Worse neighborhood socioeconomic conditions were associated with higher T2D risk, yet associations are likely not mediated through food-environment pathways.

Supplemental Figure Legend

Supplementary Fig. S1-S3, Supplementary Table S1-S9 Supplementary Fig. S1. A flow diagram of the study population. Supplementary Fig. S2. Dynamics of telomere length differs between individuals with no history of cancer and survivors of childhood cancer due to exposures to chemotherapy and/or radiation treatment. Supplementary Fig. S3. Theoretical framework of relationships among telomere length, health behaviors and chronic health conditions.

Purpose:We aimed to analyze and compare leukocyte telomere length (LTL) and age-dependent LTL attrition between childhood cancer survivors and noncancer controls, and to evaluate the associations of LTL with treatment exposures, chronic health conditions (CHC), and health behaviors among survivors.Experimental Design:We included 2,427 survivors and 293 noncancer controls of European ancestry, drawn from the participants in St. Jude Lifetime Cohort Study (SJLIFE), a retrospective hospital-based study with prospective follow-up (2007–2016). Common nonneoplastic CHCs (59 types) and subsequent malignant neoplasms (5 types) were clinically assessed. LTL was measured with whole-genome sequencing data.Results:After adjusting for age at DNA sampling, gender, genetic risk score based on 9 SNPs known to be associated with telomere length, and eigenvectors, LTL among survivors was significantly shorter both overall [adjusted mean (AM) = 6.20 kb; SE = 0.03 kb] and across diagnoses than controls (AM = 6.69 kb; SE = 0.07 kb). Among survivors, specific treatment exposures associated with shorter LTL included chest or abdominal irradiation, glucocorticoid, and vincristine chemotherapies. Significant negative associations of LTL with 14 different CHCs, and a positive association with subsequent thyroid cancer occurring out of irradiation field were identified. Health behaviors were significantly associated with LTL among survivors aged 18 to 35 years (Ptrend = 0.03).Conclusions:LTL is significantly shorter among childhood cancer survivors than noncancer controls, and is associated with CHCs and health behaviors, suggesting LTL as an aging biomarker may be a potential mechanistic target for future intervention studies designed to prevent or delay onset of CHCs in childhood cancer survivors.See related commentary by Walsh, p. 2281

PURPOSE Eight percent of young-adult childhood cancer survivors meet criteria for frailty, an aging phenotype associated with poor health. In the elderly general population, frailty is associated with neurocognitive decline; this association has not been examined in adult survivors of childhood cancer. METHODS Childhood cancer survivors 18-45 years old (≥ 10 years from diagnosis) were clinically evaluated for prefrailty or frailty (respectively defined as ≥ 2 or ≥ 3 of: muscle wasting, muscle weakness, low energy expenditure, slow walking speed, and exhaustion [Fried criteria]) and completed neuropsychologic assessments at enrollment (January 2008-June 2013) and 5 years later. Weighted linear regression using inverse of sampling probability estimates as weights compared differences in neurocognitive decline in prefrail and frail survivors versus nonfrail survivors, adjusting for diagnosis age, sex, race, CNS–directed therapy (cranial radiation, intrathecal chemotherapy, and neurosurgery), and baseline neurocognitive performance. RESULTS Survivors were on average 30 years old and 22 years from diagnosis; 18% were prefrail and 6% frail at enrollment. Frail survivors declined an average of 0.54 standard deviation (95% CI, −0.93 to −0.15) in short-term verbal recall, whereas nonfrail survivors did not decline (β = .22; difference of βs = −.76; 95% CI, −1.19 to −0.33). Frail survivors declined more than nonfrail survivors on visual-motor processing speed (β = −.40; 95% CI, −0.67 to −0.12), cognitive flexibility (β = −.62; 95% CI, −1.02 to −0.22), and verbal fluency (β = −.23; 95% CI, −0.41 to −0.05). Prefrail and frail survivors experienced greater declines in focused attention (prefrail β = −.35; 95% CI, −0.53 to −0.17; frail β = −.48; 95% CI, −0.83 to −0.12) compared with nonfrail survivors. CONCLUSION Over approximately 5 years, prefrail and frail young-adult survivors had greater declines in cognitive domains associated with aging and dementia compared with nonfrail survivors. Interventions that have global impact, designed to target the mechanistic underpinnings of frailty, may also mitigate or prevent neurocognitive decline.

Carrie R Howell,1 Caroline N Harada,2 Kevin R Fontaine,3 Michael J Mugavero,4 Andrea L Cherrington1 1Department of Medicine, Division of Preventive Medicine, University of Alabama at Birmingham, Birmingham, AL, USA; 2Department of Medicine, Division of Gerontology, Geriatrics, and Palliative Care, University of Alabama at Birmingham, Birmingham, AL, USA; 3Department of Health Behavior, School of Public Health, University of Alabama at Birmingham, Birmingham, Al, USA; 4Department of Medicine, Division of General Internal Medicine, University of Alabama at Birmingham, Birmingham, AL, USACorrespondence: Carrie R Howell, Department of Medicine, Division of Preventive Medicine, Medical Towers Suite 638, 1717 11th Avenue South, Birmingham, AL, 35294, USA, Email chowell@uabmc.eduAbstract: The evidence of suboptimal social determinants of health (SDoH) on poor health outcomes has resulted in widespread calls for research to identify ways to measure and address social needs to improve health outcomes and reduce disparities. While assessing SDoH has become increasingly important in diabetes care and prevention research, little guidance has been offered on how to address suboptimal determinants in diabetes-related clinical care, prevention efforts, medical education and research. Not surprisingly, many patients experience multiple social needs – some that are more urgent (housing) than others (transportation/resources), therefore the order in which these needs are addressed needs to be considered in the context of diabetes care/outcomes. Here we discuss how conceptualizing diabetes related health through the lens of Maslow’s hierarchy of needs has potential to help prioritize individual social needs that should be addressed to improve outcomes in the context of population-level determinants in the communities where people live.Keywords: social determinants of health, diabetes, clinical care, clinical education

Background Obesity and comorbid conditions are associated with worse outcomes related to COVID-19. Moreover, social distancing adherence during the COVID-19 pandemic may predict weight gain due to decreased physical activity, increased emotional eating, and social isolation. While early studies suggest that many individuals struggled with weight management during the pandemic, less is known about healthy eating and weight control behaviors among those enrolled in weight loss programs. Methods The present study evaluated weight management efforts among weight loss program participants during the COVID-19 pandemic. Participants’ (N = 55, 90.9% female, 36% white, Mage = 49.8) demographics and body mass index were collected two months prior to the COVID-19 statewide shutdown. During the lockdown, an online survey assessed health behaviors, coping, COVID-19 experiences (e.g., social distancing, loneliness), and weight gain. Logistic regressions examined demographics, health behaviors, and COVID-19 factors as predictors of weight gain. Results Most participants (58%) reported gaining weight during COVID-19. Weight gain was predicted by challenges with the following health behaviors: physical activity, monitoring food intake, choosing healthy foods, and emotional eating. Loneliness and working remotely significantly related to emotional eating, physical activity, and choosing healthy foods. Conclusions Loneliness and working remotely increased the difficulty of weight management behaviors during COVID-19 among weight loss program participants. However, staying active, planning and tracking food consumption, choosing healthy foods, and reducing emotional eating protected against weight gain. Thus, these factors may be key areas for weight management efforts during the pandemic.

To examine self-reported (30-day) sleep versus nightly actigraphy-assessed sleep concordance in long-term survivors of childhood cancer. Four hundred seventy-seven participants enrolled in the St. Jude Lifetime Cohort (53.5% female, median (range) age 34.3 (19.3–61.6) years, 25.4 (10.9–49.3) years from diagnosis) completed the Pittsburgh Sleep Quality Index and ≥ 3 nights of actigraphy. Participants had neurocognitive impairment and/or a self-reported prolonged sleep onset latency (SOL). Self-reported 30-day sleep and nightly actigraphic sleep measures for sleep duration, SOL, and sleep efficiency (SE) were converted into ordinal categories for calculation of weighted kappa coefficients. General linear models estimated associations between measurement concordance and late effects. Agreements between self-reported and actigraphic measures were slight to fair for sleep duration and SOL measures (kw = 0.20 and kw = 0.22, respectively; p

Diabetes self-management education and support enhance self-efficacy and promote self-management behaviors essential for diabetes management. We investigated the mediating effect of self-efficacy on the association between diabetes education or care coordination and self-care activities. We surveyed a population-based sample of adults with type 2 diabetes (19–64 years of age) covered by Alabama Medicaid. We examined whether receipt of diabetes education or care coordination were associated with improvements in diabetes self-care activities. We then examined if improvements were mediated by self-efficacy. Models were adjusted for age, gender, race, education, insulin use, diabetes duration, and depressive symptoms. Results A total of 1,318 participants were included in the study (mean age = 52.9 years, SD = 9.6; 72.5% female, 56.4% Black, 3.1% Hispanic). Diabetes education was associated with increases in self-care activity scores related to general diet, physical activity, glucose self-monitoring, and foot care; care coordination was associated with glucose self-monitoring. In addition, mediation analysis models confirmed that improvements in self-efficacy led to improved self-care activities scores, mediating the association of diabetes education and self-care activities. Conclusions Diabetes education and self-efficacy were associated with better self-care. Receiving diabetes education led to a higher likelihood of engaging in self-care activities, driven in part by increases in self-efficacy. Future interventions that aim to improve diabetes self-management behaviors can benefit from targeting self-efficacy constructs and from the integration of diabetes education in the care coordination structure.

Background Adult childhood cancer survivors are at risk for frailty, including low muscle mass and weakness (sarcopenia). Using peripheral blood mitochondrial DNA copy number (mtDNAcn) as a proxy for functional mitochondria, this study describes cross-sectional associations between mtDNAcn and sarcopenia among survivors. Methods Among 1762 adult childhood cancer survivors (51.6% male; median age = 29.4 years, interquartile range [IQR] = 23.3-36.8), with a median of 20.6 years from diagnosis (IQR = 15.2-28.2), mtDNAcn estimates were derived from whole-genome sequencing. A subset was validated by quantitative polymerase chain reaction and evaluated cross-sectionally using multivariable logistic regression for their association with sarcopenia, defined by race-, age-, and sex-specific low lean muscle mass or weak grip strength. All statistical tests were 2-sided. Results The prevalence of sarcopenia was 27.0%, higher among female than male survivors (31.5% vs 22.9%; P Conclusions A growing body of evidence supports peripheral blood mtDNAcn as a biomarker for adverse health outcomes; however, this study is the first to report an association between mtDNAcn and sarcopenia among childhood cancer survivors.

Background Some adult survivors of childhood cancers develop frailty at higher rates than expected based on their chronological age. This study examined the incidence of frailty among survivors at 10 or more years after diagnosis, frailty prevalence 5 years later, and risk factors for becoming frail. Methods Frailty was measured at study entry and 5 years later. Logistic regression tested the associations of several factors with having frailty at 5 years for all participants and separately by sex and by study entry frailty status. Cox models evaluated the hazard of death associated with entry frailty considering covariates. Results Cancer survivors (range = 0-22 years at diagnosis, median = 7 years) were ages 18-45 years (median = 30 years) at study entry. Frailty prevalence increased from 6.2% (95% confidence interval [CI] = 5.0% to 7.5%) to 13.6% (95% CI = 11.9% to 15.4%) at 5 years. Risk factors for frailty at follow-up among all survivors included chest radiation 20 Gy or higher (odds ratio [OR] = 1.98, 95% CI = 1.29 to 3.05), cardiac (OR = 1.58, 95% CI = 1.02 to 2.46), and neurological (OR = 2.58, 95% CI = 1.69 to 3.92) conditions; lack of strength training (OR = 1.74, 95% CI = 1.14 to 2.66); sedentary lifestyle (OR = 1.75, 95% CI = 1.18 to 2.59); and frailty at study entry (OR = 11.12, 95% CI = 6.64 to 18.61). The strongest risk factor for death during follow-up was prior frailty (OR = 3.52, 95% CI = 1.95 to 6.32). Conclusions Prevalent frailty more than doubled at 5 years after study entry among adult childhood cancer survivors. Frailty at entry was the strongest risk factor for death. Because treatment exposures cannot be changed, mitigation of other risk factors for frailty, including lack of strength training and sedentary lifestyle, may decrease risk of adverse health events and improve longevity in survivors.

Background: Cost-related medication nonadherence (CRMN) occurs when an individual takes less medication than what is prescribed due to difficulty affording their medications. In adults with diabetes, medication nonadherence is associated with worse glycemic control and increased healthcare costs. The goal of this study was to determine what proportion of Alabama’s Medicaid population with diabetes experiences CRMN and to evaluate for potential risk factors for CRMN in this financially-at-risk population. Methods: We conducted a cross-sectional study surveying a population-based sample of adults (ages 19-64) with diabetes covered by Alabama Medicaid. We classified participants as experiencing CRMN if they responded yes to “Not including over the counter medications, was there a time in the past 12 months when you didn't take your medication as prescribed because of cost?” Using multivariable logistic regression, we examined what variables were associated with CRMN adjusting for demographic and clinical factors (insulin use, diabetes duration, receipt of care coordination, and self-rated health) . Results: We included 1893 of 2235 (84.7%) participants who completed the survey and had complete data for the variables of interest in the analysis. This sample was predominantly nonwhite (60.7%) , female (73.9%) with a mean age of 52 ±10.1 years. Overall, 23.7% of participants reported CRMN. In the fully adjusted model, insulin use (OR 1.41, 95% CI 1.11, 1.79) , use of a discount prescription plan (OR 1.55, 95% CI 1.20, 2.00) , and self-report of poor health (OR 1.67, 95% CI 1.33, 2.09) were significantly associated with CRMN. Conclusion: We found that almost a quarter of a population-based sample of adults with diabetes covered by Alabama Medicaid experienced cost-related medication nonadherence. More research is needed to determine how to address this among this vulnerable population. Disclosure E.C.Ness: None. L.Juarez: None. C.R.Howell: None. L.Hohmann: None. A.Cherrington: Consultant; Bayer AG, Other Relationship; Novo Nordisk. C.A.Presley: None. Funding National Institute of Diabetes and Digestive and Kidney Diseases (R18DK109501) UAB Diabetes Research Center (P30 DK079626)

PURPOSE Muscle weakness, low lean body mass, and poor physical performance are prevalent among adult survivors of childhood cancer (survivors). We evaluated the feasibility and effects of resistance training with and without protein supplementation on lean body mass and muscle strength among survivors. METHODS This double-blind placebo-controlled trial enrolled survivors ≥18 to

Background: We aimed to characterize body composition, metabolic impairments, and physical performance among survivors of pediatric abdominal and pelvic solid tumors. Methods: Participants included 431 survivors of abdominal or pelvic tumors [median attained age = 29.9 (range: 18.7–55.1) years]. Relative lean mass and fat mass were assessed with dual X-ray absorptiometry. Metabolic outcomes [insulin resistance (IR), high-density lipoprotein (HDL), low-density lipoprotein, and triglycerides] were based on laboratory values and medication usage. General linear regression evaluated associations between treatment and lifestyle with body composition; binomial regression evaluated associations between body composition and metabolic outcomes and physical performance. Results: Lean mass was lower than values from the National Health and Nutrition Examination Survey (NHANES) in males (Z-score = −0.67 ± 1.27; P < 0.001) and females (Z-score = −0.72 ± 1.28; P < 0.001). Higher cumulative abdominal and pelvic radiation doses were associated with lower lean mass among males [abdominal: β = −0.22 (SE) ± 0.07; P = 0.002 and pelvic: β = −0.23 ± 0.07; P = 0.002] and females (abdominal: β = −0.30 ± 0.09; P = 0.001 and pelvic: β = −0.16 ± 0.08; P = 0.037). Prevalence of IR (40.6% vs. 33.8%; P = 0.006), low HDL (28.9% vs. 33.5%; P = 0.046), and high triglycerides (18.4% vs. 10.0%; P < 0.001) was increased among survivors relative to NHANES. Compared with survivors with normal/high lean mass and normal/low fat mass, survivors with normal/high lean mass and high fat mass had an increased risk of IR (P < 0.001), low HDL (P < 0.001), reduced quadriceps strength at 60°/second (P < 0.001) and 300°/second (P < 0.001), and reduced distance covered in the 6-minute walk (P < 0.01). Conclusions: Abdominal/pelvic radiotherapy is associated with body composition changes that can adversely influence metabolic outcomes and performance status among survivors. Impact: Interventions targeting body composition may facilitate management of cardiovascular disease risk in this population.

Introduction There is a growing population of childhood cancer survivors at risk for adverse outcomes, including sexual dysfunction. Aim To estimate the prevalence of and risk factors for sexual dysfunction among adult female survivors of childhood cancer and evaluate associations between dysfunction and psychological symptoms/quality of life (QOL). Methods Female survivors (N = 936, mean 7.8 ± 5.6 years at diagnosis; 31 ± 7.8 years at evaluation) and noncancer controls (N = 122) participating in the St. Jude Lifetime Cohort Study completed clinical evaluations, Sexual Functioning Questionnaires (SFQ), and Medical Outcomes Survey Short Forms 36 (SF-36). Linear models compared SFQ scores between sexually active survivors (N = 712) and controls; survivors with scores Outcomes Sexual dysfunction was defined by scores Results Sexual dysfunction was prevalent among 19.9% (95% CI 17.1, 23.1) of survivors. Those diagnosed with germ cell tumors (OR = 8.82, 95% CI 3.17, 24.50), renal tumors (OR = 4.49, 95% CI 1.89, 10.67), or leukemia (OR = 3.09, 95% CI 1.50, 6.38) were at greater risk compared to controls. Age at follow-up (45–54 vs 18–24 years; OR = 5.72, 95% CI 1.87, 17.49), pelvic surgery (OR = 2.03, 95% CI 1.18, 3.50), and depression (OR = 1.96, 95% CI 1.10, 3.51) were associated with sexual dysfunction. Hypogonadism receiving hormone replacement (vs nonmenopausal/nonhypogonadal; OR = 3.31, 95% CI 1.53, 7.15) represented an additional risk factor in the physical problems (eg, vaginal pain and dryness) subscale. Survivors with sexual dysfunction, compared to those without sexual dysfunction, were more likely to score Clinical Implications Health care providers should be aware of the increased risk of sexual dysfunction in this growing population, inquire about symptomology, and refer for appropriate intervention. Strengths & Limitations Strengths of this study include the use of a validated tool for evaluating sexual function in a large population of clinically assessed female childhood cancer survivors. Limitations include potential for selection bias, and lack of clinically confirmed dysfunction. Conclusion Sexual dysfunction is prevalent among female childhood cancer survivors and few survivors receive intervention; further research is needed to determine if those with sexual dysfunction would benefit from targeted interventions.

This study aimed to determine the ability of retrospective cardiometabolic disease staging (CMDS) and social determinants of health (SDoH) to predict COVID-19 outcomes.Individual and neighborhood SDoH and CMDS clinical parameters (BMI, glucose, blood pressure, high-density lipoprotein, triglycerides), collected up to 3 years prior to a positive COVID-19 test, were extracted from the electronic medical record. Bayesian logistic regression was used to model CMDS and SDoH to predict subsequent hospitalization, intensive care unit (ICU) admission, and mortality, and whether adding SDoH to the CMDS model improved prediction was investigated. Models were cross validated, and areas under the curve (AUC) were compared.A total of 2,873 patients were identified (mean age: 58 years [SD 13.2], 59% were female, 45% were Black). CMDS, insurance status, male sex, and higher glucose values were associated with increased odds of all outcomes; area-level social vulnerability was associated with increased odds of hospitalization (odds ratio: 1.84, 95% CI: 1.38-2.45) and ICU admission (odds ratio 1.98, 95% CI: 1.45-2.85). The AUCs improved when SDoH were added to CMDS (p 0.001): hospitalization (AUC 0.78 vs. 0.82), ICU admission (AUC 0.77 vs. 0.81), and mortality (AUC 0.77 vs. 0.83).Retrospective clinical markers of cardiometabolic disease and SDoH were independently predictive of COVID-19 outcomes in the population.

Objective To describe the real-world deployment of a tool, the Protocol for Responding to and Assessing Patients’ Assets, Risks, and Experiences (PRAPARE), to assess social determinants of health (SDoH) in an electronic medical record (EMR). Methods We employed the collection of the PRAPARE tool in the EMR of a large academic health system in the ambulatory clinic and emergency department setting. After integration, we evaluated SDoH prevalence, levels of missingness, and data anomalies to inform ongoing collection. We summarized responses using descriptive statistics and hand-reviewed data text fields and patterns in the data. Data on patients who were administered with the PRAPARE from February to December 2020 were extracted from the EMR. Patients missing ≥ 12 PRAPARE questions were excluded. Social risks were screened using the PRAPARE. Information on demographics, admittance status, and health coverage were extracted from the EMR. Results Assessments with N = 6531 were completed (mean age 54 years, female (58.6%), 43.8% Black). Missingness ranged from 0.4% (race) to 20.8% (income). Approximately 6% of patients were homeless; 8% reported housing insecurity; 1.4% reported food needs; 14.6% had healthcare needs; 8.4% needed utility assistance; and 5% lacked transportation related to medical care. Emergency department patients reported significantly higher proportions of suboptimal SDoH. Conclusions Integrating the PRAPARE assessment in the EMR provides valuable information on SDoH amenable to intervention, and strategies are needed to increase accurate data collection and to improve the use of data in the clinical encounter.

Including race as a biological construct in risk prediction models may guide clinical decisions in ways that cause harm and widen racial disparities. This study reports on using race versus social determinants of health (SDoH) in predicting the associations between cardiometabolic disease severity (assessed using cardiometabolic disease staging) and COVID-19 hospitalization.Electronic medical record data on patients with a positive COVID-19 polymerase chain reaction test in 2020 and a previous encounter in the electronic medical record where cardiometabolic disease staging clinical data (BMI, blood glucose, blood pressure, high-density lipoprotein cholesterol, and triglycerides) were available from 2017 to 2020, were analyzed in 2021. Associations between cardiometabolic disease staging and COVID-19 hospitalization adding race and SDoH (individual and neighborhood level [e.g., Social Vulnerability Index]) in different models were examined. Area under the curve was used to assess predictive performance.A total of 2,745 patients were included (mean age of 58 years, 59% female, 47% Black). In the cardiometabolic disease staging model, area under the curve was 0.767 vs 0.777 when race was included. Adding SDoH to the cardiometabolic model improved the area under the curve to 0.809 (p0.001), whereas the addition of SDoH and race increased the area under the curve to 0.811. In race-stratified models, the area under the curve for non-Hispanic Blacks was 0.781, whereas the model for non-Hispanic Whites performed better with an area under the curve of 0.821.Cardiometabolic disease staging was predictive of hospitalization after a positive COVID-19 test. Adding race did not markedly increase the predictive ability; however, adding SDoH to the model improved the area under the curve to ≥0.80. Future research should include SDoH with biological variables in prediction modeling to capture social experience of race.

Background Adult survivors of childhood cancer are at risk of developing sleep and neurocognitive problems, yet few efficacious interventions exist targeting these prevalent late effects. Melatonin has known sleep-promoting effects; however, it has not been well studied among childhood cancer survivors. Method Survivors (n = 580; mean age = 33.5 years; 26 years post-diagnosis) from the St. Jude Lifetime Cohort were randomized (1:1) to a six-month double-blind placebo-controlled trial of 3 mg time-release melatonin within three strata (stratum 1: neurocognitive impairment only; stratum 2: neurocognitive and sleep impairment; stratum 3: sleep impairment only). Neurocognitive performance was assessed at baseline and post-intervention using standardized measures. Sleep was assessed via self-report and actigraphy. Independent sample t tests compared mean change scores from baseline to six months. Post-hoc analyses compared the prevalence of clinically significant treatment responders among melatonin and placebo conditions within and across strata. Results Intent-to-treat analyses revealed no statistically significant differences in neurocognitive performance or sleep from baseline to post-intervention. However, among survivors with neurocognitive impairment only, a larger proportion randomized to melatonin versus placebo demonstrated a treatment response for visuomotor speed (63% vs 41%, P = 0.02) and nonverbal reasoning (46% vs 28%, P = 0.04). Among survivors with sleep impairment only, a larger proportion treated with melatonin demonstrated a treatment response for shifting attention (44% vs 28%, P = 0.05), short-term memory (39% vs 19%, P = 0.01), and actigraphy-assessed sleep duration (47% vs 29%, P = 0.05). Conclusion Melatonin was not associated with improved neurocognitive performance or sleep in our intent-to-treat analyses; however, a subset of survivors demonstrated a clinically significant treatment response.

Background Among adult childhood cancer survivors, the relationship between race/ethnicity and health insurance status, as a contributor to disparities in healthcare utilization, is poorly understood. Methods We examined racial/ethnic-related disparities by insurance status in “forgoing needed medical care in the last year due to finances” using 3,964 adult childhood cancer survivors (3310 non-Hispanic/Latinx White, 562 non-Hispanic/Latinx Black, and 92 Hispanic/Latinx) participating in the St. Jude Lifetime Cohort Study (SJLIFE). Multivariable logistic regression analyses, guided by Andersen’s Healthcare Utilization Model, were adjusted for “predisposing” (age, sex, childhood cancer diagnosis, cancer treatment, surgery, and treatment era) and “need” (perceived health status) factors. Additional adjustment for income/education and chronic health conditions was considered. Results The risk of forgoing care was highest among non-Hispanic/Latinx Blacks and lowest among Hispanics/Latinxs for each insurance status. Among privately-insured survivors, relative to non-Hispanic/Latinx Whites, non-Hispanic/Latinx Blacks were more likely to forgo care (adjusted OR: 1.82, 95% CI: 1.30–2.54): this disparity remained despite additional adjustment for income/education (adjusted OR: 1.43, 95% CI: 1.01–2.01). In contrast, publicly-insured survivors, regardless of race/ethnicity, had similar risk of forgoing care as privately-insured non-Hispanic/Latinx Whites. All uninsured survivors had high risk of forgoing care. Additional adjustment for chronic health conditions did not alter these results. Conclusions The findings of this study show that provision of public insurance to all childhood cancer survivors may diminish racial/ethnic disparities in forgoing care that exist among the privately-insured and reduce the risk of forgoing care among uninsured survivors to that of privately-insured non-Hispanic/Latinx Whites. Key messages Providing publicly funded health insurance coverage to childhood cancer survivors can reduce disparities in forgoing medical care.

Cardiovascular disease is up to 10 times more likely among childhood cancer survivors compared to siblings. Low cardiorespiratory fitness is a modifiable risk-factor for cardiovascular diseases. Yet, cardiorespiratory fitness is not routinely screened in pediatric oncology, and healthy VO2max cut-points are unavailable. We aimed to predict cardiorespiratory fitness by developing a simple algorithm and establish cut-points identifying survivors' cardiovascular fitness health-risk zones. We recruited 262 childhood cancer survivors (8-18 years old, ≥1-year posttreatment). Participants completed gold-standard cardiorespiratory fitness assessment (Cardiopulmonary Exercise Test [CPET; VO2max ]) and 6-minute walk test (6MWT). Associations with VO2max were included in a linear regression algorithm to predict VO2max , which was then cross-validated. We used Bland-Altman's limits of agreement and Receiver Operating Characteristic curves using FITNESSGRAM's "Healthy Fitness Zones" to identify cut-points for adequate cardiorespiratory fitness. A total of 199 participants (aged 13.7 ± 2.7 years, 8.5 ± 3.5 years posttreatment) were included. We found a strong positive correlation between VO2max and 6MWT distance (r = 0.61, r2 = 0.37, p

Background Greater than one-half of children who are treated for acute lymphoblastic leukemia (ALL) develop ≥1 treatment-related medical conditions in their lifetime, many of which are known risk factors for diabetes mellitus. In the current study, the authors evaluated the prevalence and risk factors of diabetes mellitus among clinically assessed adult survivors of childhood ALL METHODS: The authors performed a retrospective evaluation of data from survivors of ALL and community controls who were enrolled in the St. Jude Lifetime Cohort Study between October 1, 2007, and June 30, 2016. Participants were adults with ≥10 years of survival of childhood ALL and community controls who completed clinical and laboratory evaluations. Data for the current analysis were abstracted from medical records. Exposures evaluated herein included chemotherapy and radiation exposures and medical history, including drug-induced diabetes mellitus. Results Of 1360 eligible adults who were ≥10-year survivors of childhood ALL, a total of 1044 completed the evaluations; these individuals had a mean age of 33.97±9.14 years and 50.86% were male. The 368 controls, 45.65% of whom were male, had a mean age of 35.33±10.21 years. Type 2 diabetes mellitus (T2DM) was found in approximately 7.47% of survivors and 3.80% of controls (odds ratio [OR], 2.07; 95% CI, 1.11-3.87). In adjusted models, among survivors, older age (OR, 1.05 for each additional year; 95% CI, 1.02-1.08), body mass index ≥30 kg/m2 (OR, 7.40; 95% CI, 2.61-20.97), and drug-induced diabetes mellitus occurring during ALL therapy (OR, 4.67; 95% CI, 2.53-8.61) were found to be associated with T2DM. Conclusions Adult survivors of childhood ALL are at an increased risk of T2DM. Adult survivors of childhood ALL who are of older age, with an overweight or obese body mass index, and/or who developed drug-induced diabetes mellitus during treatment should be closely monitored for T2DM during long-term follow-up.

BACKGROUND Survivors of childhood acute lymphoblastic leukemia (ALL) are at increased risk for both treatment-related exercise intolerance and neurocognitive deficits. This analysis aimed to identify the association between exercise intolerance and neurocognitive impairments in ALL survivors. METHODS Cardiopulmonary exercise testing, results from a 2-hour standardized neuropsychological assessment, and self-report questionnaires were obtained for 341 adult survivors of childhood ALL and 288 controls. Multivariable modeling was used to test associations between oxygen uptake at 85% estimated heart rate (rpkVO2 ) and neuropsychological test and self-reported questionnaire domains, adjusted for sex, age at diagnosis, cranial radiation, anthracycline, and methotrexate exposure and tobacco smoking status. RESULTS Compared with controls, survivors had worse rpkVO2 and performance on verbal intelligence, focused attention, verbal fluency, working memory, dominant/nondominant motor speed, visual-motor speed, memory span, and reading and math measures (all P

BACKGROUND Limited data exist regarding left ventricular remodeling patterns observed in adult survivors of childhood cancer after therapy. METHODS Among 1190 adult survivors diagnosed with childhood cancer (median age at diagnosis, 9 years [interquartile range (IQR), 3.8-14.4 years]; age at evaluation, 35.6 years [IQR, 29.5-42.8 years]), treatment exposures included anthracyclines (n = 346), chest radiotherapy (n = 174), both (n = 245), or neither (n = 425). Prospective echocardiographic assessment compared survivors with 449 noncancer controls classified according to left ventricle geometric patterns. Associations between left ventricle geometric patterns and decreased exercise tolerance were assessed. RESULTS Overall, 28.2% of survivors (95% confidence interval [CI], 25.6%-30.8%) exhibited concentric remodeling, 2.4% (95% CI, 1.6%-3.5%) exhibited eccentric hypertrophy, and 1.1% (95% CI, 0.6%-1.9%) exhibited concentric hypertrophy. A greater proportion of survivors who received only chest radiotherapy (41%) had concentric remodeling compared with those who received only anthracyclines (24%), both (27%), or neither (27%; all P < .001), and all were greater than the proportions in noncancer controls (18%; all P < .05). Concentric remodeling was associated with radiation exposure, but not with anthracycline exposure, in multivariable models. Survivors who had concentric remodeling were more likely to have a maximal oxygen uptake peak

Background Daily self-weighing (DSW) may be an effective harm-reduction intervention to disrupt continued weight gain. S elf- W eighing for O besity Management in P rimary Care (SWOP) is a 24-month randomized controlled trial in 400 adults with obesity (BMI: kg/m2 ≥ 30) receiving primary care through a clinical network affiliated with an academic medical center. Objective To test DSW as a potentially scalable way to deter age-related weight gain among primary care patients with obesity. Methods Randomized-controlled trial with two conditions: DSW (instruction to weigh daily and provision of a web-enabled digital scale with graphical weight feedback) or Standard Care (receive a monetary gift card equivalent to value of the scale). Both groups receive standardized weight management educational material. SWOP will test the causal effect of assignment to DSW (Aim 1) and adherence to DSW (Aim 2) on weight (primary outcome) and adoption of weight management practices (secondary outcomes), as well as evaluate the cost-effectiveness of DSW compared to standard care (Aim 3). Findings may inform clinical guidelines for weight management by providing evidence that DSW attenuates continued age-related weight gain among adults with obesity. This trial is registered with ClinicalTrials.gov (NCT04044794).

PURPOSE: To investigate racial/ethnic-related disparities by insurance status in “forgoing needed medical care in the last year due to finances” in childhood cancer survivors. METHODS: Our study included 3310 non-Hispanic/Latinx White, 562 non-Hispanic/Latinx Black, and 92 Hispanic/Latinx survivors from the St. Jude Lifetime Cohort Study. Logistic regression analyses, guided by Andersen’s Healthcare Utilization Model, were adjusted for “predisposing” (survey age, sex, childhood cancer diagnosis and treatment, and treatment era) and “need” (perceived health status) factors. Additional adjustment for household income/education and chronic health conditions was considered. RESULTS: Risk of forgoing care was highest among non-Hispanic/Latinx Blacks and lowest among Hispanics/Latinxs for each insurance status. Among privately insured survivors, relative to non-Hispanic/Latinx Whites, non-Hispanic/Latinx Blacks were more likely to forgo care (adjusted OR: 1.82, 95% CI: 1.30–2.54): this disparity remained despite additional adjustment for household income/education (adjusted OR: 1.43, 95% CI: 1.01–2.01). In contrast, publicly insured survivors, regardless of race/ethnicity, had similar risk of forgoing care as privately insured non-Hispanic/Latinx Whites. All uninsured survivors had high risk of forgoing care. Additional chronic health condition adjustment did not alter these results. CONCLUSIONS: Provision of public insurance to all childhood cancer survivors may diminish racial/ethnic disparities in forgoing care that exist among the privately insured and reduce the risk of forgoing care among uninsured survivors to that of privately insured non-Hispanic/Latinx Whites. IMPLICATIONS FOR CANCER SURVIVORS: Under public insurance, childhood cancer survivors had low risk of forgoing care, at the similar level to privately insured non-Hispanic/Latinx Whites, regardless of race/ethnicity.

To examine self-reported (30-day) sleep versus nightly actigraphy-assessed sleep concordance in long-term survivors of childhood cancer.Four hundred seventy-seven participants enrolled in the St. Jude Lifetime Cohort (53.5% female, median (range) age 34.3 (19.3-61.6) years, 25.4 (10.9-49.3) years from diagnosis) completed the Pittsburgh Sleep Quality Index and ≥ 3 nights of actigraphy. Participants had neurocognitive impairment and/or a self-reported prolonged sleep onset latency (SOL). Self-reported 30-day sleep and nightly actigraphic sleep measures for sleep duration, SOL, and sleep efficiency (SE) were converted into ordinal categories for calculation of weighted kappa coefficients. General linear models estimated associations between measurement concordance and late effects.Agreements between self-reported and actigraphic measures were slight to fair for sleep duration and SOL measures (kSelf-reported sleep and actigraphic sleep demonstrated discordance in our sample. Several prevalent late effects were statistically significantly associated with increased measurement discrepancy. Future studies should consider the impacts of late effects on sleep assessment in adult survivors of childhood cancer.

BACKGROUND Survivors of childhood cancer exposed to cardiotoxic therapies are at significant cardiovascular risk. The utility of cardiac biomarkers for identifying the risk of future cardiomyopathy and mortality is unknown. METHODS N-terminal pro-B-type natriuretic peptide (NT-proBNP) and cardiac troponin T (cTnT) were assessed in 1213 adults 10 or more years from a childhood cancer diagnosis; 786 were exposed to anthracycline chemotherapy and/or chest-directed radiation therapy (RT). NT-proBNP values above age- and sex-specific 97.5th percentiles were considered abnormal. Generalized linear models estimated cross-sectional associations between abnormal NT-proBNP and anthracycline or chest RT doses as risk ratios with 95% confidence intervals (CIs). A Poisson distribution estimated rates and a Cox proportional hazards model estimated hazard ratios (HRs) for future cardiac events and death. RESULTS At a median age of 35.5 years (interquartile range, 29.8-42.5 years), NT-proBNP and cTnT were abnormal in 22.5% and 0.4%, respectively. Exposure to chest RT and exposure to anthracycline chemotherapy were each associated with a dose-dependent increased risk for abnormal NT-proBNP (P for trend

Summary With mounting interest in translating genome-wide association study (GWAS) hits from large meta-analyses (meta-GWAS) in diverse clinical settings, evaluating their generalizability in target populations is crucial. Here, we consider long-term survivors of childhood cancers from the St. Jude Lifetime Cohort Study, and we show the limited generalizability of 1,376 robust SNP associations reported in the general population across 12 complex anthropometric and cardiometabolic phenotypes (n = 2,231; observed-to-expected replication ratio = 0.70, p = 6.2 × 10−8). An examination of five comparable phenotypes in a second independent cohort of survivors from the Childhood Cancer Survivor Study corroborated the overall limited generalizability of meta-GWAS hits to survivors (n = 4,212; observed-to-expected replication ratio = 0.55, p = 5.6 × 10−15). Finally, in direct comparisons of survivor samples against independent equivalently powered general population samples from the UK Biobank, we consistently observed lower meta-GWAS hit replication rates and poorer polygenic risk score predictive performance in survivor samples for multiple phenotypes. As a possible explanation, we found that meta-GWAS hits were less likely to be replicated in survivors who had been exposed to cancer therapies that are associated with phenotype risk. Examination of complementary DNA methylation data in a subset of survivors revealed that treatment-related methylation patterns at genomic sites linked to meta-GWAS hits may disrupt established genetic signals in survivors.

Background Most studies among Hispanics have focused on individual risk factors of obesity, with less attention on interpersonal, community and environmental determinants. Conducting community based surveys to study these determinants must ensure representativeness of disparate populations. We describe the use of a novel Geographic Information System (GIS)-based population based sampling to minimize selection bias in a rural community based study. Methods We conducted a community based survey to collect and examine social determinants of health and their association with obesity prevalence among a sample of Hispanics and non-Hispanic whites living in a rural community in the Southeastern United States. To ensure a balanced sample of both ethnic groups, we designed an area stratified random sampling procedure involving three stages: (1) division of the sampling area into non-overlapping strata based on Hispanic household proportion using GIS software; (2) random selection of the designated number of Census blocks from each stratum; and (3) random selection of the designated number of housing units (i.e., survey participants) from each Census block. Results The proposed sample included 109 Hispanic and 107 non-Hispanic participants to be recruited from 44 Census blocks. The final sample included 106 Hispanic and 111 non-Hispanic participants. The proportion of Hispanic surveys completed per strata matched our proposed distribution: 7% for strata 1, 30% for strata 2, 58% for strata 3 and 83% for strata 4. Conclusion Utilizing a standardized area based randomized sampling approach allowed us to successfully recruit an ethnically balanced sample while conducting door to door surveys in a rural, community based study. The integration of area based randomized sampling using tools such as GIS in future community-based research should be considered, particularly when trying to reach disparate populations.

Background In noncancer populations, insomnia is known to affect neurocognitive processes. Although the prevalence of insomnia appears to be elevated in survivors of childhood cancer, relatively little is known about its association with neurocognitive performance in this at-risk population. Methods A total of 911 survivors (51.9% female; mean [SD] age, 34 [9.0] years; time since diagnosis, 26 [9.1] years) completed direct assessments of attention, memory, processing speed, and executive functioning and self-reported symptoms of sleep (Pittsburgh Sleep Quality Index), fatigue (Functional Assessment of Chronic Illness Therapy-Fatigue), and daytime sleepiness (Epworth Sleepiness Scale). Sex-stratified general linear models were used to examine associations between insomnia and neurocognitive performance, with adjustment for treatment exposures and chronic health conditions. All statistical tests were two-sided. Results Insomnia was reported by 22.1% of females and 12.3% of males (P Conclusions Insomnia was highly prevalent and contributed to the neurocognitive burden experienced by adult survivors of childhood cancer. Treatment of insomnia may improve neurocognitive problems in survivors.

The purpose of this study was to define the prevalence of and risk factors for elevated serum alanine aminotransferase (ALT) level among adult childhood cancer survivors (CCS). The study cohort comprised 2,751 CCS from the St. Jude Lifetime Cohort Study (>10 years postdiagnosis, age ≥18 years). Serum ALT level was graded using the Common Terminology Criteria for Adverse Events v. 4.03. Modified Poisson regression models were used to estimate relative risks and 95% confidence intervals for the association between demographic and clinical factors and grades 1-4 ALT on the selected models. A total of 1,339 (48.7%) CCS were female; 2,271 (82.6%) were non-Hispanic white. Median age at evaluation was 31.4 years (interquartile range [IQR] = 25.8-37.8); median elapsed time from diagnosis to evaluation was 23.2 years (IQR = 17.6-29.7). A total of 1,137 (41.3%) CSS had ALT > upper limit of normal (Common Terminology Criteria for Adverse Events v. 4.03 grade 1-1,058 (38.5%); grade 2-56 (2.0%); grade 3-23 (0.8%); grade 4-none). Multivariable models demonstrated non-Hispanic white race/ethnicity, age at evaluation in years, being overweight or obese, presence of the metabolic syndrome, current treatment with atorvastatin or rosuvastatin or simvastatin, hepatitis C virus infection, prior treatment with busulfan or thioguanine, history of hepatic surgery, and the percentage of liver treated with ≥10 Gray, ≥15 Gray, or ≥20 Gray were associated with elevated ALT. Conclusion: Grade 3 or 4 hepatic injury is infrequent in CCS. Mild hepatic injury in this group may be amenable to lifestyle modifications.

Objective Epidemiologic analyses indicate a lack of association between body mass index (BMI: kg/m2) and mortality among Hispanic adults. Because BMI provides only a surrogate for the real variable of interest (adiposity), we evaluated associations between measures of body composition and mortality. Methods Using data from US-residing Mexican-Americans in the National Health and Nutrition Examination Survey (NHANES) III (n=4,480) and NHANES 1999–2010 (n=5,849), we examined the association between seven measures of body composition measured via anthropometry and bio-electrical impedance analysis (i.e., waist circumference, waist-to-height ratios (WHtR), skinfolds, lean mass, fat mass, percent body fat and BMI) and all-cause and cardiovascular and diabetes mortality. We conducted additional analyses stratified by gender. Results Waist circumference (hazard ratio [HR] 1.04, 95% Confidence Interval (CI): 1.01, 1.07) and WHtR (HR: 1.08, 95% CI: 1.03–1.14) were weakly associated with an increased all-cause mortality, while WHtR was associated with an increased risk of diabetes-related death (HR: 1.26, 95% CI: 1.07–1.49). In gender stratified analyses, we observed increases in risk of mortality in females who had increases in WHtR and waist circumference for all-cause mortality and cardiovascular deaths. Conclusion Waist circumference and WHtR were associated with increased risk of all-cause and diabetes-related mortality in US-residing Mexican-American adults.

Purpose To compare peripheral nervous system function and balance between adult survivors of childhood acute lymphoblastic leukemia (ALL) and matched controls and to determine associations between peripheral neuropathy (PN) and limitations in static balance, mobility, walking endurance, and quality of life (QoL) among survivors. Patients and Methods Three hundred sixty-five adult survivors of childhood ALL and 365 controls with no cancer history completed assessments of PN (modified Total Neuropathy Score [mTNS]), static balance (Sensory Organization Test [SOT]), mobility (Timed Up and Go), walking endurance (6-minute walk test), QoL (Medical Outcomes Study 36-Item Short Form Survey), and visual-motor processing speed (Wechsler Adult Intelligence Scale). Results PN, but not impairments, in performance on SOT was more common in survivors than controls (41.4% v 9.5%, respectively; P < .001). In multivariable models, higher mTNS scores were associated with longer time to complete the Timed Up and Go (β = 0.15; 95% CI, 0.06 to 0.23; P < .001), shorter distance walked in 6 minutes (β = −4.39; 95% CI, −8.63 to −0.14; P = .04), and reduced QoL (β = −1.33; 95% CI, −1.79 to −0.87; P < .001 for physical functioning; β = −1.16; 95% CI, −1.64 to −0.67; P < .001 for role physical; and β = −0.88; 95% CI, −1.34 to −0.42; P < .001 for general health). Processing speed (β = 1.69; 95% CI, 0.98 to 2.40; P < .001), but not mTNS score, was associated with anterior-posterior sway on the SOT. Conclusion PN in long-term ALL survivors is associated with movement, including mobility and walking endurance, but not with static standing balance. The association between processing speed and sway suggests that static balance impairment in ALL survivors may be influenced by problems with CNS function, including the processing of sensory information.

The population of adult survivors of childhood cancer continues to grow as survival rates improve. Although it is well established that these survivors experience various complications and comorbidities related to their malignancy and treatment, this risk is modified by many factors that are not directly linked to their cancer history. Research evaluating the influence of patient-specific demographic and genetic factors, premorbid and comorbid conditions, health behaviors, and aging has identified additional risk factors that influence cancer treatment-related toxicity and possible targets for intervention in this population. Furthermore, although current long-term follow-up guidelines comprehensively address specific therapy-related risks and provide screening recommendations, the risk profile of the population continues to evolve with ongoing modification of treatment strategies and the emergence of novel therapeutics. To address the multifactorial modifiers of cancer treatment-related health risk and evolving treatment approaches, a patient-centered and risk-adapted approach to care that often requires a multidisciplinary team approach, including medical and behavioral providers, is necessary for this population. CA Cancer J Clin 2018;68:133-152. © 2018 American Cancer Society.

BACKGROUND Sedentary behaviors are associated with poor health outcomes in the general population, but their clinical impact on adult survivors of childhood acute lymphoblastic leukemia (ALL) has not been characterized to date. In the current study, we described the prevalence of sedentary behaviors in survivors of ALL and examined associations between time spent sedentary and body composition and onset of cardiovascular disease (CVD) risk factors. METHODS Participants' self-reported screen time (eg, television, computer) and activity as measured by accelerometer were used to determine activity time (sedentary, light activity, and moderate or vigorous physical activity). The percentage of time spent in each activity was compared between 331 survivors of ALL and 330 controls. Associations between time sedentary and body composition were evaluated in survivors using linear regression models. Cox proportional hazard models were used to examine the association between time sedentary at baseline and CVD risk factor onset during follow-up. RESULTS Survivors spent approximately 65% of their time sedentary, 32% in light activity, and 2% in moderate or vigorous physical activity compared with 67% (P = .04), 30% (P

Summary Background Survivors of childhood cancer develop early and severe chronic health conditions (CHCs). A quantitative landscape of morbidity of survivors, however, has not been described. We aimed to describe the cumulative burden of curative cancer therapy in a clinically assessed ageing population of long-term survivors of childhood cancer. Methods The St Jude Lifetime Cohort Study (SJLIFE) retrospectively collected data on CHCs in all patients treated for childhood cancer at the St Jude Children's Research Hospital who survived 10 years or longer from initial diagnosis and were 18 years or older as of June 30, 2015. Age-matched and sex-frequency-matched community controls were used for comparison. 21 treatment exposure variables were included in the analysis, with data abstracted from medical records. 168 CHCs for all participants were graded for severity using a modified Common Terminology Criteria of Adverse Events. Multiple imputation with predictive mean matching was used for missing occurrences and grades of CHCs in the survivors who were not clinically evaluable. Mean cumulative count was used for descriptive cumulative burden analysis and marked-point-process regression was used for inferential cumulative burden analysis. Findings Of 5522 patients treated for childhood cancer at St Jude Children's Research Hospital who had complete records, survived 10 years or longer, and were 18 years or older at time of study, 3010 (54·5%) were alive, had enrolled, and had had prospective clinical assessment. 2512 (45·5%) of the 5522 patients were not clinically evaluable. The cumulative incidence of CHCs at age 50 years was 99·9% (95% CI 99·9–99·9) for grade 1–5 CHCs and 96·0% (95% CI 95·3–96·8%) for grade 3–5 CHCs. By age 50 years, a survivor had experienced, on average, 17·1 (95% CI 16·2–18·1) CHCs of any grade, of which 4·7 (4·6–4·9) were CHCs of grade 3–5. The cumulative burden in matched community controls of grade 1–5 CHCs was 9·2 (95% CI 7·9–10·6; p vs total study population) and of grade 3–5 CHCs was 2·3 (1·9–2·7, p vs total study population). Second neoplasms, spinal disorders, and pulmonary disease were major contributors to the excess total cumulative burden. Notable heterogeneity in the distribution of CHC burden in survivors with differing primary cancer diagnoses was observed. The cumulative burden of grade 1–5 CHCs at age 50 years was highest in survivors of CNS malignancies (24·2 [95% CI 20·9–27·5]) and lowest in survivors of germ cell tumours (14·0 [11·5–16·6]). Multivariable analyses showed that older age at diagnosis, treatment era, and higher doses of brain and chest radiation are significantly associated with a greater cumulative burden and severity of CHCs. Interpretation The burden of CHCs in survivors of childhood cancer is substantial and highly variable. Our assessment of total cumulative burden in survivors of paediatric cancer, with detailed characterisation of long-term CHCs, provide data to better inform future clinical guidelines, research investigations, and health services planning for this vulnerable, medically complex population. Funding The US National Cancer Institute, St Baldrick's Foundation, and the American Lebanese Syrian Associated Charities.

Purpose: We aimed to analyze and compare leukocyte telomere length (LTL) and age-dependent LTL attrition between childhood cancer survivors and noncancer controls, and to evaluate the associations of LTL with treatment exposures, chronic health conditions (CHC), and health behaviors among survivors. Experimental Design: We included 2,427 survivors and 293 noncancer controls of European ancestry, drawn from the participants in St. Jude Lifetime Cohort Study (SJLIFE), a retrospective hospital-based study with prospective follow-up (2007–2016). Common nonneoplastic CHCs (59 types) and subsequent malignant neoplasms (5 types) were clinically assessed. LTL was measured with whole-genome sequencing data. Results: After adjusting for age at DNA sampling, gender, genetic risk score based on 9 SNPs known to be associated with telomere length, and eigenvectors, LTL among survivors was significantly shorter both overall [adjusted mean (AM) = 6.20 kb; SE = 0.03 kb] and across diagnoses than controls (AM = 6.69 kb; SE = 0.07 kb). Among survivors, specific treatment exposures associated with shorter LTL included chest or abdominal irradiation, glucocorticoid, and vincristine chemotherapies. Significant negative associations of LTL with 14 different CHCs, and a positive association with subsequent thyroid cancer occurring out of irradiation field were identified. Health behaviors were significantly associated with LTL among survivors aged 18 to 35 years (Ptrend = 0.03). Conclusions: LTL is significantly shorter among childhood cancer survivors than noncancer controls, and is associated with CHCs and health behaviors, suggesting LTL as an aging biomarker may be a potential mechanistic target for future intervention studies designed to prevent or delay onset of CHCs in childhood cancer survivors. See related commentary by Walsh, p. 2281

PURPOSE Anthracycline-associated risk for subsequent breast cancer in childhood cancer survivors is hypothesized to be mediated by TP53 mutation-related gene-environment interactions. We characterized treatment/genetic risks and the impact of screening for breast cancer in the St Jude Lifetime Cohort. PATIENTS AND METHODS Female participants underwent risk-based assessments, prior health event validation, chest radiation dosimetry, and whole genome sequencing. Breast biopsy reports were reviewed. A subgroup (n = 139) underwent both breast magnetic resonance imaging and mammography. Multivariable regression was used to calculate hazard ratios (HRs) and 95% CIs. RESULTS Among 1,467 women, 56 developed 68 breast cancers at a median age 38.6 (range, 24.5 to 53.0) years. Cumulative incidences at age 35 years were 1% (no chest radiation) and 8% (≥ 10 Gy of chest radiation). In adjusted models, breast cancer was associated with 20 Gy or more of chest radiation versus none (HR, 7.6; 95% CI, 2.9 to 20.4), anthracycline exposure versus none (1 to 249 mg/m2: HR, 2.6; 95% CI, 1.1 to 6.2; ≥ 250 mg/m2: HR, 13.4, 95% CI, 5.5 to 32.5), and having a breast cancer predisposition gene mutation (HR, 23.0; 95% CI, 7.3 to 72.2). Anthracyclines 250 mg/m2 or greater remained significantly associated with increased risk of breast cancer in models excluding survivors with cancer predisposition gene mutations, chest radiation 10 Gy or greater, or both. Sensitivity/specificity were 53.8%/96.3% for mammography, 69.2%/91.4% for magnetic resonance imaging, and 85.8%/99.7% for dual imaging. Breast cancers detected by imaging and/or prophylactic mastectomy compared with physical findings were more likely to be in situ carcinomas, smaller, without lymph node involvement, and treated without chemotherapy. CONCLUSION Higher doses of anthracyclines are associated with increased risk of breast cancer independent of mutations in known cancer predisposition genes. Surveillance imaging identifies breast cancers less likely to require chemotherapy than those detected by physical findings.

10017 Background: Racial, ethnic, and socioeconomic disparities are documented in outcomes for childhood cancer survivors. Understanding whether childhood cancer modifies established disparities in cardiovascular risk factors (CVRFs) in the general population would inform strategies to reduce health inequities among survivors. Methods: The CCSS is a retrospectively constructed cohort with prospective follow-up consisting of 25,579 five year survivors of childhood cancer diagnosed between 1970 and 1999. We estimated the incidence of self-reported Common Terminology Criteria for Adverse Events (CTCAE) grade >2 CVRFs (hypertension, diabetes, dyslipidemia, and obesity) and multiple (>2) CVRFs among survivors. Multivariable Poisson regression estimated the rate ratios (RR) of CVRFs by race/ethnicity, adjusted for key treatment exposures and sociodemographics. Results: Within the CCSS cohort, there were 20,416 non-Hispanic White (NHW), 1625 non-Hispanic Black (NHB), and 2043 Hispanic survivors with the cumulative incidence estimates of each CVRF at age 40 displayed in Table. Survivors who self-reported “Other” or mixed race were excluded for this analysis (n=1495). NHB survivors were more likely to report hypertension (unadjusted RR 1.3; 95% Confidence Interval [CI] 1.0-1.6), diabetes (RR 1.6; 95% CI 1.0-2.4), obesity (RR 1.6; 95% CI 1.4-1.9), and multiple CVRF (RR 1.3; 95% CI 1.2-1.5), whereas Hispanic survivors were more likely to report diabetes (RR 1.7; 95% CI 1.2-2.4), obesity (RR 1.4; 95% CI 1.2-1.5), and multiple CVRFs (RR 1.1; 95% CI 1.0-1.3) compared with NHW survivors. These observed disparities in risks of CVRFs remained nearly unchanged even after adjustment for sociodemographic factors (age, sex, household income, education, marital status, employment, and insurance) and treatment exposures (Yes/No for anthracyclines, alkylators, and chest radiation). Conclusions: NHB and Hispanic adult survivors demonstrate a higher burden of CVRF compared with NHW survivors, particularly diabetes and obesity. The associated morbidity of these conditions and established increase they incur in risk of more severe cardiovascular disease emphasizes the need for interventions to mitigate CVRFs to promote health equity among these survivors.[Table: see text]