Hispanic Ethnicity and Fertility Outcomes.

OBJECTIVE: To assess the association between ethnicity and fertility outcomes for men in a statewide cohort. DESIGN: We linked data from the Utah Population Database (UPDB) and Subfertility Health Assisted Reproduction and Environment (SHARE) database, to comprise a cohort of sub-fertile men who underwent semen analysis (SA) between 1998-2017 in Utah. A multivariable Cox proportional hazard model was constructed to understand the impact of ethnicity on fertility outcomes in our cohort. RESULTS: 11,363 men were included. 1,039 (9.1%) were Hispanic. 39.7% of men in the lowest socioeconomic status group (SES) were Hispanic (p<0.001). When controlling for demographic and clinical factors, the number of live births was reduced for Hispanic men (HR=0.62 [0.57-0.67], p<0.001). Though fertility treatment (FT) had a positive effect (HR 1.242 [1.085-1.421], p<0.001), in competing risks models, Hispanic men were less likely to use FT (HR=0.633 [0.526-0.762], p<0.001). CONCLUSION: Hispanic ethnicity is significantly associated with a lower likelihood of successful fertility outcomes in Utah. Hispanic men had nearly a 40% reduced likelihood of live births when controlling for sociodemographic factors. Our results indicate that, depending on age, Hispanic men have up to approximately 14 fewer live births per 100 men per year, pointing to a significant disparity in fertility outcomes in the state of Utah. Given 15.1% of Utah's population identifies as Hispanic and 18.7% of the United States population identifies as Hispanic on the 2020 Census, better understanding of the association of ethnicity and fertility outcomes is imperative.

Describing patterns of familial cancer risk in subfertile men using population pedigree data.

STUDY QUESTION: Can we simultaneously assess risk for multiple cancers to identify familial multicancer patterns in families of azoospermic and severely oligozoospermic men? SUMMARY ANSWER: Distinct familial cancer patterns were observed in the azoospermia and severe oligozoospermia cohorts, suggesting heterogeneity in familial cancer risk by both type of subfertility and within subfertility type. WHAT IS KNOWN ALREADY: Subfertile men and their relatives show increased risk for certain cancers including testicular, thyroid, and pediatric. STUDY DESIGN, SIZE, DURATION: A retrospective cohort of subfertile men (N = 786) was identified and matched to fertile population controls (N = 5674). Family members out to third-degree relatives were identified for both subfertile men and fertile population controls (N = 337 754). The study period was 1966-2017. Individuals were censored at death or loss to follow-up, loss to follow-up occurred if they left Utah during the study period. PARTICIPANTS/MATERIALS, SETTING, METHODS: Azoospermic (0 × 106/mL) and severely oligozoospermic (<1.5 × 106/mL) men were identified in the Subfertility Health and Assisted Reproduction and the Environment cohort (SHARE). Subfertile men were age- and sex-matched 5:1 to fertile population controls and family members out to third-degree relatives were identified using the Utah Population Database (UPDB). Cancer diagnoses were identified through the Utah Cancer Registry. Families containing ≥10 members with ≥1 year of follow-up 1966-2017 were included (azoospermic: N = 426 families, 21 361 individuals; oligozoospermic: N = 360 families, 18 818 individuals). Unsupervised clustering based on standardized incidence ratios for 34 cancer phenotypes in the families was used to identify familial multicancer patterns; azoospermia and severe oligospermia families were assessed separately. MAIN RESULTS AND THE ROLE OF CHANCE: Compared to control families, significant increases in cancer risks were observed in the azoospermia cohort for five cancer types: bone and joint cancers hazard ratio (HR) = 2.56 (95% CI = 1.48-4.42), soft tissue cancers HR = 1.56 (95% CI = 1.01-2.39), uterine cancers HR = 1.27 (95% CI = 1.03-1.56), Hodgkin lymphomas HR = 1.60 (95% CI = 1.07-2.39), and thyroid cancer HR = 1.54 (95% CI = 1.21-1.97). Among severe oligozoospermia families, increased risk was seen for three cancer types: colon cancer HR = 1.16 (95% CI = 1.01-1.32), bone and joint cancers HR = 2.43 (95% CI = 1.30-4.54), and testis cancer HR = 2.34 (95% CI = 1.60-3.42) along with a significant decrease in esophageal cancer risk HR = 0.39 (95% CI = 0.16-0.97). Thirteen clusters of familial multicancer patterns were identified in families of azoospermic men, 66% of families in the azoospermia cohort showed population-level cancer risks, however, the remaining 12 clusters showed elevated risk for 2-7 cancer types. Several of the clusters with elevated cancer risks also showed increased odds of cancer diagnoses at young ages with six clusters showing increased odds of adolescent and young adult (AYA) diagnosis [odds ratio (OR) = 1.96-2.88] and two clusters showing increased odds of pediatric cancer diagnosis (OR = 3.64-12.63). Within the severe oligozoospermia cohort, 12 distinct familial multicancer clusters were identified. All 12 clusters showed elevated risk for 1-3 cancer types. An increase in odds of cancer diagnoses at young ages was also seen in five of the severe oligozoospermia familial multicancer clusters, three clusters showed increased odds of AYA diagnosis (OR = 2.19-2.78) with an additional two clusters showing increased odds of a pediatric diagnosis (OR = 3.84-9.32). LIMITATIONS, REASONS FOR CAUTION: Although this study has many strengths, including population data for family structure, cancer diagnoses and subfertility, there are limitations. First, semen measures are not available for the sample of fertile men. Second, there is no information on medical comorbidities or lifestyle risk factors such as smoking status, BMI, or environmental exposures. Third, all of the subfertile men included in this study were seen at a fertility clinic for evaluation. These men were therefore a subset of the overall population experiencing fertility problems and likely represent those with the socioeconomic means for evaluation by a physician. WIDER IMPLICATIONS OF THE FINDINGS: This analysis leveraged unique population-level data resources, SHARE and the UPDB, to describe novel multicancer clusters among the families of azoospermic and severely oligozoospermic men. Distinct overall multicancer risk and familial multicancer patterns were observed in the azoospermia and severe oligozoospermia cohorts, suggesting heterogeneity in cancer risk by type of subfertility and within subfertility type. Describing families with similar cancer risk patterns provides a new avenue to increase homogeneity for focused gene discovery and environmental risk factor studies. Such discoveries will lead to more accurate risk predictions and improved counseling for patients and their families. STUDY FUNDING/COMPETING INTEREST(S): This work was funded by GEMS: Genomic approach to connecting Elevated germline Mutation rates with male infertility and Somatic health (Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD): R01 HD106112). The authors have no conflicts of interest relevant to this work. TRIAL REGISTRATION NUMBER: N/A.

Transgenerational effects of paternal exposures: the role of germline de novo mutations.

Germline de novo mutations (DNMs) refer to spontaneous mutations arising during gametogenesis, resulting in genetic changes within germ cells that are subsequently transmitted to the next generation. While the impact of maternal exposures on germline DNMs has been extensively studied, more recent studies have begun to highlight the increasing importance of the effects of paternal factors. In this review, we have summarized the existing literature on how various exposures experienced by fathers affect the germline DNM burden in their spermatozoa, as well as their consequences for semen analysis parameters, pregnancy outcomes, and offspring health. A growing body of literature supports the conclusion that advanced paternal age (APA) correlates with a higher germline DNM rate in offspring. Furthermore, lifestyle choices, environmental toxins, assisted reproductive techniques (ART), and chemotherapy are associated with the accumulation of paternal DNMs in spermatozoa, with deleterious consequences for pregnancy outcomes and offspring health. Ultimately, our review highlights the clear importance of the germline DNM mode of inheritance, and the current understanding of how this is affected by various paternal factors. In addition, we explore conflicting reports or gaps of knowledge that should be addressed in future research.

The association between parental age differences and perinatal outcomes.

STUDY QUESTION: Are there significant associations existing between parental age differences and adverse perinatal outcomes? SUMMARY ANSWER: Large differences in parental age are associated with adverse perinatal outcomes, particularly with older mothers paired with younger fathers. WHAT IS KNOWN ALREADY: The association between advanced maternal age and perinatal outcomes is well-documented with women over 35 years showing an increased risk of several adverse outcomes. Other studies have identified potential associations between advanced paternal age and adverse perinatal outcomes. STUDY DESIGN, SIZE, DURATION: A historical (retrospective) cohort analysis was performed utilizing a multivariable logistic regression model to evaluate the association between varying differences in parental age and adverse perinatal outcomes while controlling for demographic and health-related covariates. Data were compiled from the National Vital Statistics System for 20 613 704 births between 2012 and 2018. PARTICIPANTS/MATERIALS, SETTING, METHODS: Parental age differences, categorized into eleven 4-year intervals, were stratified by seven maternal age categories and evaluated for their associations with adverse perinatal outcomes. Main outcome measures included low birth weight, very low birth weight, preterm birth, very preterm birth, small size for gestational age, low 5-min appearance, pulse, grimace, activity, and respiration score, congenital defects, and chromosomal anomalies. MAIN RESULTS AND THE ROLE OF CHANCE: Increased parental age differences, in either direction, were associated with significant risks for all adverse outcomes, aside from congenital defects, even when controlling for maternal age. Restricting maternal age to the reference range of 25-29 years, infants born to fathers aged 9-12 years younger (n = 3773) had 27% (odds ratio (OR) 1.27, 95% CI, 1.17-1.37) higher odds of having any adverse perinatal outcome. Infants born to fathers aged >16 years older (n = 98 555) had 14% (OR 1.14, 95% CI, 1.12-1.16) higher odds of having any adverse perinatal outcome. LIMITATIONS, REASONS FOR CAUTION: Data extracted from US birth certificates may be compromised by errors in reporting or documentation. Information regarding the mother's socioeconomic status was estimated using proxy variables and may be susceptible to uncontrolled factors. Use of a pre-compiled dataset may potentially exclude additional maternal comorbidities that could impact perinatal outcomes. WIDER IMPLICATIONS OF FINDINGS: Older mothers paired with younger fathers demonstrated the highest risk, even when maternal age was below the threshold of 35 years. For the clinical setting, parental age differences should be considered alongside maternal and paternal age when assessing risks of adverse perinatal outcomes for potential parents. This is particularly relevant for older women with younger male partners as this may exacerbate the impact of advanced maternal age. STUDY FUNDING/COMPETING INTEREST(S): This research was funded by the NIH Research Fellowship T35 Training Grant. There are no competing interests. TRIAL REGISTRATION NUMBER: N/A.

Diverticulitis Familiality: A Statewide Case-Control Study.

BACKGROUND: The etiology of diverticulitis is multifactorial and poorly understood. We estimated the familiality of diverticulitis using the Utah Population Database, a statewide database linking medical records with genealogy data. STUDY DESIGN: We identified patients with diverticulitis diagnosed between 1998 and 2018 and age- and sex-matched controls in the Utah Population Database. Risk of diverticulitis in family members of patients and controls was calculated using multivariable Poisson models. We performed exploratory analyses to determine the association of familial diverticulitis with severity of disease and age of onset. RESULTS: The study population included 9,563 diverticulitis patients (with 229,647 relatives) and 10,588 controls (with 265,693 relatives). Relatives of patients were more likely to develop diverticulitis (incidence rate ratio [IRR] 1.5, 95% CI 1.4 to 1.6) compared with relatives of controls. There was an elevated risk of diverticulitis among first-degree (IRR 2.6, 95% CI 2.3 to 3.0), second-degree (IRR 1.5, 95% CI 1.3 to 1.6), and third-degree relatives of patients (IRR 1.3, 95% CI 1.2 to 1.4). Complicated diverticulitis was more common among relatives of patients compared with relatives of controls (IRR 1.6, 95% CI 1.4 to 1.8). Age at diverticulitis diagnosis was similar between groups (relatives of patients 0.2 years older than relatives of controls, 95% CI -0.5 to 0.9). CONCLUSIONS: Our results indicate that the first-, second-, and third-degree relatives of diverticulitis patients are at elevated risk of developing diverticulitis. This information may aid surgeons in counseling patients and family members about diverticulitis risk and can inform the development of future risk-stratification tools. Further work is needed to clarify the causal role and relative contribution of various genetic, lifestyle, and environmental factors in the development of diverticulitis.

Environmental exposure to industrial air pollution is associated with decreased male fertility.

OBJECTIVE: To understand how chronic exposure to industrial air pollution is associated with male fertility through semen parameters. DESIGN: Retrospective cohort study. PATIENTS: Men in the Subfertility, Health, and Assisted Reproduction cohort who underwent a semen analysis in the two largest healthcare systems in Utah from 2005-2017 with ≥1 measured semen parameter (N = 21,563). INTERVENTION(S): Residential histories for each man were constructed using locations from administrative records linked through the Utah Population Database. Industrial facilities with air emissions of nine endocrine-disrupting compound chemical classes were identified from the Environmental Protection Agency Risk-Screening Environmental Indicators microdata. Chemical levels were linked with residential histories for the 5 years before each semen analysis. MAIN OUTCOME MEASURES: Semen analyses were classified as azoospermic or oligozoospermic (< 15 M/mL) using World Health Organization cutoffs for concentration. Bulk semen parameters such as concentration, total count, ejaculate volume, total motility, total motile count, and total progressive motile count were also measured. Multivariable regression models with robust standard errors were used to associate exposure quartiles for each of the nine chemical classes with each semen parameter, adjusting for age, race, and ethnicity, as well as neighborhood socioeconomic disadvantage. RESULTS: After adjustment for demographic covariates, several chemical classes were associated with azoospermia and decreased total motility and volume. For exposure in the 4th relative to 1st quartile, significant associations were observed for acrylonitrile (ßtotal motility = -0.87 pp), aromatic hydrocarbons (odds ratio [OR]azoospermia = 1.53; ßvolume = -0.14 mL), dioxins (ORazoospermia = 1.31; ßvolume = -0.09 mL; ßtotal motility = -2.65 pp), heavy metals (ßtotal motility = -2.78pp), organic solvents (ORazoospermia = 1.75; ßvolume = -0.10 mL), organochlorines (ORazoospermia = 2.09; ßvolume = -0.12 mL), phthalates (ORazoospermia = 1.44; ßvolume = -0.09 mL; ßtotal motility = -1.21 pp), and silver particles (ORazoospermia = 1.64; ßvolume = -0.11 mL). All semen parameters significantly decreased with increasing socioeconomic disadvantage. Men who lived in the most disadvantaged areas had concentration, volume, and total motility of 6.70 M/mL, 0.13 mL, and 1.79 pp lower, respectively. Count, motile count, and total progressive motile count all decreased by 30-34 M. CONCLUSION(S): Several significant associations between chronic low-level environmental exposure to endocrine-disrupting compound air pollution from industrial sources and semen parameters were observed. The strongest associations were seen for increased odds of azoospermia and declines in total motility and volume. More research is needed to further explore additional social and exposure factors as well as expand on the risk posed to male reproductive health by the studied chemicals.

Risk Factors and Trends for HPV-Associated Subsequent Malignant Neoplasms among Adolescent and Young Adult Cancer Survivors.

BACKGROUND: Subsequent malignant neoplasms (SMN; new cancers that arise after an original diagnosis) contribute to premature mortality among adolescent and young adult (AYA) cancer survivors. Because of the high population prevalence of human papillomavirus (HPV) infection, we identify demographic and clinical risk factors for HPV-associated SMNs (HPV-SMN) among AYA cancer survivors in the SEER-9 registries diagnosed from 1976 to 2015. METHODS: Outcomes included any HPV-SMN, oropharyngeal-SMN, and cervical-SMN. Follow-up started 2 months after their original diagnosis. Standardized incidence ratios (SIR) compared risk between AYA survivors and general population. Age-period-cohort (APC) models examined trends over time. Fine and Gray's models identified therapy effects controlling for cancer and demographic confounders. RESULTS: Of 374,408 survivors, 1,369 had an HPV-SMN, occurring on average 5 years after first cancer. Compared with the general population, AYA survivors had 70% increased risk for any HPV-SMN [95% confidence interval (CI), 1.61-1.79] and 117% for oropharyngeal-SMN (95% CI, 2.00-2.35); cervical-SMN risk was generally lower in survivors (SIR, 0.85; 95% CI, 0.76-0.95), but Hispanic AYA survivors had a 8.4 significant increase in cervical-SMN (SIR, 1.46; 95% CI, 1.01-2.06). AYAs first diagnosed with Kaposi sarcoma, leukemia, Hodgkin, and non-Hodgkin lymphoma had increased HPV-SMN risks compared with the general population. Oropharyngeal-SMN incidence declined over time in APC models. Chemotherapy and radiation were associated with any HPV-SMN among survivors with first HPV-related cancers, but not associated among survivors whose first cancers were not HPV-related. CONCLUSIONS: HPV-SMN in AYA survivors are driven by oropharyngeal cancers despite temporal declines in oropharyngeal-SMN. Hispanic survivors are at risk for cervical-SMN relative to the general population. IMPACT: Encouraging HPV vaccination and cervical and oral cancer screenings may reduce HPV-SMN burden among AYA survivors.

COVID-19-Related Employment Disruptions and Increased Financial Burden Among Survivors of Adolescent and Young Adult Cancer.

Background: Financial burden is a major concern for survivors of adolescent and young adult (AYA) cancers. We identified if employment disruptions during the COVID-19 pandemic affected AYA survivors' financial burden. Methods: AYAs who were enrolled in a cancer patient navigation program were e-mailed a survey in fall 2020. Survey items included sociodemographics, employment disruption, and two measures of financial burden: COmprehensive Score for Financial Toxicity (COST) and material and behavioral financial hardship items (for any reason, COVID-19 induced, cancer induced). Financial burden outcomes were dichotomized at the median (COST = 21; financial hardship = 3). The association of employment disruptions and sociodemographics with financial burden was assessed using multivariable logistic regression models. Results: Reduced hours/job loss was reported by 24.0% of 341 participants. Survivors with a high school education or less (odds ratio [OR]: 2.70; 95% confidence interval [CI]: 1.21-6.03) or who had decreased hours or job loss (OR: 3.97; 95% CI: 2.01-7.84) had greater odds for high financial toxicity. Reduced hours/job loss was the only factor associated with high material and behavioral financial hardship for both any reason (OR: 2.75; 95% CI: 1.41-5.33) and owing to COVID-19 (OR: 4.98; 95% CI: 2.28-10.92). Cancer treatment since March 2020 was associated with cancer-induced high material and behavioral financial hardship (OR: 3.31; 95% CI: 1.96-5.58). Conclusion: Employment disruptions owing to the COVID-19 pandemic, lower education levels, and cancer treatment were associated with high financial burden among AYA cancer survivors. Our findings suggest the need for multilevel interventions to identify and address financial burden among vulnerable cancer survivors.

The impact of socioeconomic status on bulk semen parameters, fertility treatment, and fertility outcomes in a cohort of subfertile men.

OBJECTIVE: To study the effect of socioeconomic status on the use of fertility treatment and the rate of live birth in men with subfertility. DESIGN: A retrospective, time-to-event analysis of men with subfertility in Utah stratified by socioeconomic status. SETTING: Patients seen in fertility clinics throughout Utah. PATIENT(S): All men in Utah undergoing semen analysis between 1998 and 2017 at the state's 2 largest health care networks. INTERVENTION(S): Socioeconomic status (defined as area deprivation index of patients' residential location). MAIN OUTCOME MEASURE(S): Categorical use of fertility treatment, the count of fertility treatments (in patients with ≥1 treatment), and live birth after semen analysis. RESULT(S): When controlling for age, ethnicity, and semen parameters (count and concentration), men from low socioeconomic areas were only 60%-70% as likely to use fertility treatment depending on type compared with men from high socioeconomic areas (intrauterine insemination [IUI] hazards ratio [HR] = 0.691 (0.581-0.821), P<.001; in vitro fertilization [IVF] HR = 0.602 (0.466-0.778), P<.001). Of men undergoing fertility treatment, those from low socioeconomic areas had 75%-80% the number of treatments as men from high socioeconomic areas depending on type (IUI incident rate ratio = 0.740 (0.645-0.847), P<.001; IVF incident rate ratios = 0.803 (0.585-1.094), P=.170). When controlling for age, ethnicity, semen parameters, and use of fertility treatment, men from low socioeconomic areas were only 87% as likely to experience a live birth as men from high socioeconomic areas (HR = 0.871 (0.820-0.925), P<.001). Given the overall higher likelihood of live birth in men from high socioeconomic areas, as well as their greater chance of using fertility treatment, we predicted an annual disparity of 5 additional live births in high socioeconomic men compared with low for every 100 men. CONCLUSION(S): Men from low socioeconomic areas undergoing semen analyses are significantly less likely to use fertility treatment and experience a live birth than their counterparts from high socioeconomic areas. Mitigation programs to increase access to fertility treatment may help to reduce this bias; however, our results suggest that additional discrepancies beyond fertility treatment require addressing.

Patterns of indoor radon concentrations, radon-hazard potential, and radon testing on a small geographic scale in Utah.

INTRODUCTION: Currently, there are no publicly-available estimates of indoor radon concentration at scales smaller than the county. Radon-hazard potential soil maps that reflect underlying geologic factors can be created at small geographic scale and linked to residential and census data. We determined the association between residential radon tests and high radon-hazard potential soil at the residential and block group levels using a large Utah-based dataset. We also identified characteristics of block groups with limited tests in the dataset. METHODS: We geocoded a dataset of residential radon tests obtained from 2001 to 2017 by a statewide educational program. We linked each location to maps of radon-hazard potential soil, the Environmental Protection Agency's (EPA) county radon zones. We also calculated the number of tests conducted in each block group and linked block groups to demographic data from the 2020 United States census. Log-linear and logistic models identified the association between residential home test results and 1) radon-hazard potential soil of each residence, 2) percent of residences on high radon-hazard potential soils in block groups, and 3) EPA's radon zones. We compared demographic characteristics among block groups with ≥5 or <5 residential tests in our dataset. RESULTS: Approximately 42% of homes in the dataset tested ≥4 pCi/L. We found significant positive associations for residential radon test results with 1) residential location on high radon-hazard potential soil and 2) block groups with >0% of residences on high radon-hazard potential soil. EPA radon zones were not associated with residential test results. Block groups with <5 tests had higher than the statewide median percentage of Hispanic residents (OR = 2.46, 95% CI = 1.89-3.21) and were located in rural counties. DISCUSSION: Radon-hazard potential soil has a significant association with residential home radon tests. More efforts are needed to improve radon testing in block groups that are rural and have greater percentages of racial minorities.

HPV Vaccination Initiation and Completion Among Pediatric, Adolescent, and Young Adult Cancer Survivors and a Comparison Population Sample Receiving Primary Care.

Human papillomavirus (HPV) vaccinations can reduce pediatric, adolescent, and young adult (PAYA) cancer survivors' susceptibility to HPV-related subsequent cancers. We examined differences in HPV vaccination initiation and completion among a Utah-based cohort of PAYA cancer survivors and a cancer-free population sample. Participants received primary care at 1 of 2 health care systems during study follow-up: 2006-2016. Vaccination records were identified from these health care systems, statewide vaccination records, and an all-payer claims database. HPV vaccination initiation (1 dose) and completion (3 doses) were compared between cancer survivors (N=1579) and age-matched and sex-matched cancer-free population sample (N=4513). Individuals were 9 to 21 years old at cohort entry. Mixed-effects Poisson regression estimated incidence rate ratios (IRRs) and 95% confidence intervals (CIs). Relative to the population sample, cancer survivors were less likely to initiate vaccination (IRR=0.8, 95% CI: 0.73-0.98). The most severe disparity compared with the population sample for vaccine initiation (IRR=0.5, 95% CI: 0.31-0.74) or completion (IRR=0.5, 95% CI: 0.28-0.89) was observed for Hispanic survivors. PAYA cancer survivors are less likely to initiate HPV vaccination series than noncancer counterparts. Targeted interventions should be directed at PAYA survivors to raise HPV vaccination with emphasis on high-risk groups such as Hispanic survivors.

Missed opportunities for concomitant HPV vaccination among childhood cancer survivors.

PURPOSE: Childhood cancer survivors are at higher risk of human papillomavirus (HPV)-related second cancers than adolescents without cancer, yet their HPV vaccination uptake is lower. Using a statewide sample, we evaluated whether survivors are at higher risk of missed opportunities for concomitant HPV vaccination. METHODS: From statewide healthcare data, we identified encounters where vaccines were received. Concomitant HPV vaccine missed opportunities were defined as a vaccine encounter where the HPV vaccine was not administered, although eligibility criteria were met. From these encounters, our sample included 327 survivors identified from the Utah Cancer Registry, diagnosed 2000-2016 at ages 0-9, and a birth year and sex-matched sample without cancer from the general population (n = 1,911). Mixed-effects Poisson regression estimated the rate of concomitant missed opportunities per vaccine encounter and 95% confidence intervals by vaccine encounter type (all vaccines, flu shot only, or adolescent/catch-up) from 2013 to 2016. RESULTS: Survivors had more concomitant HPV vaccine missed opportunities than the population sample (70.0% vs. 59.0%). On average, survivors were 12% more likely to have missed opportunities at vaccine encounters and 4% more likely at flu shot only encounters. The predicted excess risk of concomitant missed opportunities for survivors ranged from 0.5 per10 vaccine encounters to 1.1 per10 vaccine encounters. Higher parental education, rurality, younger first vaccine age, and chemotherapy were associated with missed opportunities. CONCLUSIONS: Childhood cancer survivors have more missed opportunities for concomitant HPV vaccination than a population sample. As flu shots should be administered annually, providers have a regular opportunity to recommend and deliver the HPV vaccine to survivors.

COVID-19 Vaccine Hesitancy Among Adolescent and Young Adult Cancer Survivors.

The study objective was to identify sociodemographic and coronavirus disease 2019 (COVID-19) factors that are associated with COVID-19 vaccine hesitancy among adolescent and young adult (AYA) cancer survivors. Eligible participants were 18 years or older and were diagnosed with cancer as an AYA (ages 15-39 years) and received services through an AYA cancer program. A total of 342 participants completed a cross-sectional survey. Our primary outcome-COVID-19 vaccine hesitancy-was surveyed as a 5-point Likert scale and operationalized as a binary outcome (agree vs hesitant). A large proportion of participants reported COVID-19 vaccine hesitancy (37.1%). In the multivariable regression, female survivors (odds ratio = 1.81, 95% confidence interval = 1.10 to 2.98) and survivors with a high school education or less (odds ratio = 3.15, 95% confidence interval = 1.41 to 7.04) reported higher odds of vaccine hesitancy compared with their male or college graduate or higher counterparts. COVID-19 vaccine hesitancy persists among AYA survivors despite their recommended priority vaccination status and higher chances of severe COVID-19 outcomes.

Fine Particulate Matter Air Pollution and Mortality among Pediatric, Adolescent, and Young Adult Cancer Patients.

BACKGROUND: Air pollution is a carcinogen and causes pulmonary and cardiac complications. We examined the association of fine particulate matter pollution (PM2.5) and mortality from cancer and all causes among pediatric, adolescent, and young adult (AYA) patients with cancer in Utah, a state with considerable variation in PM2.5. METHODS: We followed 2,444 pediatric (diagnosed ages 0-14) and 13,459 AYA (diagnosed ages 15-39) patients diagnosed in 1986-2015 from diagnosis to 5 and 10 years postdiagnosis, death, or emigration. We measured average monthly PM2.5 by ZIP code during follow-up. Separate pediatric and AYA multivariable Cox models estimated the association of PM2.5 and mortality. Among AYAs, we examined effect modification of PM2.5 and mortality by stage while controlling for cancer type. RESULTS: Increases in PM2.5 per 5 µg/m3 were associated with cancer mortality in pediatric lymphomas and central nervous system (CNS) tumors at both time points, and all cause mortality in lymphoid leukemias [HR5-year = 1.32 (1.02-1.71)]. Among AYAs, PM2.5 per 5 µg/m3 was associated with cancer mortality in CNS tumors and carcinomas at both time points, and all cause mortality for all AYA cancer types [HR5-year = 1.06 (1.01-1.13)]. PM2.5 ≥12 µg/m3 was associated with cancer mortality among breast [HR5-year = 1.50 (1.29-1.74); HR10-year = 1.30 (1.13-1.50)] and colorectal cancers [HR5-year = 1.74 (1.29-2.35); HR10-year = 1.67 (1.20-2.31)] at both time points. Effect modification by stage was significant, with local tumors at highest risk. CONCLUSIONS: PM2.5 was associated with mortality in pediatric and AYA patients with specific cancers. IMPACT: Limiting PM2.5 exposure may be important for young cancer patients with certain cancers.See all articles in this CEBP Focus section, "Environmental Carcinogenesis: Pathways to Prevention."

Hospitalization after Adolescent and Young Adult (AYA) Cancer: A Population-Based Study in Utah.

BACKGROUND: Adolescents and young adults (AYA, age 15-39 years) with cancer may be at elevated risk for late morbidity following their cancer treatment, but few studies have quantified the excess burden of severe disease in this population. Using population-based data from Utah, we examined the risk of inpatient hospitalizations among AYA cancer survivors compared with their siblings and the general population. METHODS: Survivors of AYA cancer who were ≥2 years from diagnosis and diagnosed from 1994 to 2015 (N = 6,330), their siblings (N = 12,924), and an age- and sex-matched comparison cohort (N = 18,171) were identified using the Utah Population Database (UPDB). Hospitalizations from 1996 to 2017 were identified from statewide discharge records in the UPDB. We estimated multivariable-adjusted hazard ratios (HR) for first hospitalization and rate ratios (RR) for total hospitalizations for survivors relative to the matched comparison cohort and siblings. RESULTS: Overall, the risk of a first hospitalization was higher among AYA cancer survivors than the matched population-based cohort [HR = 1.93; 95% confidence interval (CI), 1.81-2.06]. Risk was most elevated for survivors of leukemia (HR = 4.76), central nervous system tumors (HR = 3.45), colorectal cancers (HR = 2.83), non-Hodgkin lymphoma (HR = 2.76), and breast cancer (HR = 2.37). The rate of total hospitalizations was also increased among survivors relative to the comparison cohort (RR = 2.05; 95% CI, 1.95-2.14). Patterns were generally similar in analyses comparing survivors to their siblings. CONCLUSIONS: AYA cancer survivors have a higher burden of inpatient hospitalization than their siblings and the general population. IMPACT: Results indicate the importance of long-term, risk-based follow-up care to prevent and treat severe morbidities after cancer treatment.

Validity of retrospective occupational exposure estimates of lead and manganese in a case-control study.

OBJECTIVES: The validity of surrogate measures of retrospective occupational exposure in population-based epidemiological studies has rarely been evaluated. Using toenail samples as bioindicators of exposure, we assessed whether work tasks and expert assessments of occupational metal exposure obtained from personal interviews were associated with lead and manganese concentrations. METHODS: We selected 609 controls from a case-control study of bladder cancer in New England who had held a job for ≥1 year 8-24 months prior to toenail collection. We evaluated associations between toenail metal concentrations and five tasks extracted from occupational questionnaires (grinding, painting, soldering, welding, working near engines) using linear regression models. For 139 subjects, we also evaluated associations between the toenail concentrations and exposure estimates from three experts. RESULTS: We observed a 1.9-fold increase (95% CI 1.4 to 2.5) in toenail lead concentrations with painting and 1.4-fold increase (95% CI 1.1 to 1.7) in manganese concentrations with working around engines and handling fuel. We observed significant trends with increasing frequency of both activities. For lead, significant trends were observed with the ratings from all three experts. Their average ratings showed the strongest association, with subjects rated as possibly or probably exposed to lead having concentrations that were 2.0 and 2.5 times higher, respectively, than in unexposed subjects (ptrend <0.001). Expert estimates were only weakly associated with manganese toenail concentrations. CONCLUSIONS: Our findings support the ability of experts to identify broad contrasts in previous occupational exposure to lead. The stronger associations with task frequency and expert assessments support using refined exposure characterisation whenever possible.

Fine Particulate Matter and Respiratory Healthcare Encounters among Survivors of Childhood Cancers.

Some chemotherapies that treat childhood cancers have pulmonary-toxic properties that increase risk for adverse respiratory-health outcomes. PM2.5 causes similar outcomes but its effect among pulmonary compromised cancer survivors is unknown. This case-crossover study identified the PM2.5-associated odds for primary-respiratory hospitalizations and emergency department visits among childhood cancer survivors in Utah. We compared risk among chemotherapy-treated survivors to a cancer-free sample. We calculated 3-day-average PM2.5 by ZIP code and county for event and control days. Conditional logistic regression estimated odds ratios. Models were stratified by cause of admission (infection, respiratory disease, asthma), previous chemotherapy, National Ambient Air Quality Standard (NAAQS), and other variables. Results are presented per 10 µg/m³ of PM2.5. 90% of events occurred at 3-day PM2.5 averages <35.4 µg/m³, the NAAQS 24-h standard. For survivors, PM2.5 was associated with respiratory hospitalizations (OR = 1.84, 95% CI = 1.13⁻3.00) and hospitalizations from respiratory infection (OR = 2.09, 95% CI = 1.06⁻4.14). Among chemotherapy-treated survivors, the PM2.5-associated odds of respiratory hospitalization (OR = 2.03, 95% CI = 1.14⁻3.61) were significantly higher than the cancer-free sample (OR = 0.84, 95% CI = 0.57⁻1.25). This is the first study to report significant associations between PM2.5 and respiratory healthcare encounters in childhood cancer survivors. Chemotherapy-treated survivors displayed the highest odds of hospitalization due to PM2.5 exposure and their risk is significantly higher than a cancer-free sample.

Respiratory emergency department use from diagnosis through survivorship in children, adolescents, and young adults with cancer.

BACKGROUND: Children and adolescents and young adults (AYAs) with cancer often experience severe respiratory morbidity and mortality from the therapies used to treat their cancers. Few studies have examined respiratory outcomes among this population using emergency department (ED) visits as an objective measure of respiratory health. METHODS: ED visits for respiratory conditions were identified for children and AYAs diagnosed with cancer, 0-25 years of age, from 1997 through 2012 (2535 cases) and compared with a birthdate-matched and sex-matched cohort without cancer drawn from the general population (7605 controls). Negative binomial regression with robust standard errors was used to estimate incidence rates, rate ratios (RRs), and 95% confidence intervals for primary respiratory ED visits, combined and by diagnosis (asthma, respiratory disease, and respiratory infection) from 1997 through 2015. Analyses were performed for new cases (0 to <5 years from diagnosis) and survivors (5-18 years from diagnosis). RESULTS: Subjects were followed for an average of 8 years (range, 0-18 years). Relative to the comparison cohort, cancer cases had higher incidence rates for all types of respiratory ED visits over both follow-up times. New cases had significantly higher RRs for any respiratory condition (RR, 4.14), respiratory disease (RR, 4.62), and respiratory infection (RR, 4.74). Among survivors, the RRs for any respiratory condition (RR, 2.00) and respiratory infection (RR, 2.10) were significantly elevated, although the magnitude tended to decline in survivorship. Demographic and clinical risk factors found to be associated with respiratory ED visits included Hispanic/other race/ethnicity, male sex, exposure to chemotherapy, diagnosis at a younger age, and a diagnosis of leukemia. CONCLUSIONS: The results of the current study demonstrated that children and AYAs with cancer face an increased burden of respiratory complications compared with a comparison cohort without cancer from diagnosis through survivorship.

Follow-Up Care Provider Preferences of Adolescent and Young Adult Cancer Survivors.

PURPOSE: To explore the experiences and perspectives of adolescent and young adult (AYA) cancer survivors regarding patient-provider relationships and their preferences surrounding type of healthcare provider for follow-up care. METHODS: We recruited AYA cancer survivors who were diagnosed between the ages of 15 and 39 using the Utah Cancer Registry. Twenty-eight survivors participated in six focus groups held between March and May of 2015 in Salt Lake City and St. George, Utah. This analysis focuses on how survivors' preferences about type of healthcare provider may influence their transition into, and utilization of, follow-up care. RESULTS: On average, survivors were 6.3 (standard deviation = 1.7) years from their cancer diagnosis. A majority of survivors expressed a desire not to transition to a new provider and preferred continuing to see their oncologist for follow-up care. For these survivors, this was due to already having a close relationship with their oncologist and because they trusted their provider's knowledge about cancer and how to handle late effects. However, survivors placed emphasis on being comfortable with their healthcare provider, regardless of provider type. CONCLUSIONS: Our findings demonstrate the importance of formalizing provider transitions and roles after cancer therapy to improve patient comfort with new providers. By understanding the complexities of the transition from active cancer treatment to follow-up care for AYA survivors, these findings can inform programs undertaking post-care educational activities to ensure a seamless transition into survivorship care. Survivorship care plans can facilitate these transitions and improve patient confidence in follow-up care.