Newborn Screening for Li-Fraumeni Syndrome: Patient Perspectives.

Background: Li-Fraumeni syndrome (LFS) is an inherited cancer predisposition syndrome with an estimated prevalence of 1 in 3,000-5,000 individuals. LFS poses a significant cancer risk throughout the lifespan, with notable cancer susceptibility in childhood. Despite being predominantly inherited, up to 20% of cases arise de novo. Surveillance protocols facilitate the reduction of mortality and morbidity through early cancer detection. While newborn screening (NBS) has proven effective in identifying newborns with rare genetic conditions, even those occurring as rarely as 1 in 185,000, its potential for detecting inherited cancer predispositions remains largely unexplored. Methods: This survey-based study investigates perspectives toward NBS for LFS among individuals with and parents of children with LFS receiving care at single comprehensive cancer center in the U.S. Results: All participants unanimously supported NBS for LFS (n = 24). Reasons included empowerment (83.3%), control (66.7%), and peace of mind (54.2%), albeit with concerns about anxiety (62.5%) and devastation (50%) related to receiving positive results. Participants endorsed NBS as beneficial for cancer detection and prevention (91.7%), research efforts (87.5%), and family planning (79.2%) but voiced apprehensions about the financial cost of cancer surveillance (62.5%), emotional burdens (62.5%), and insurance coverage and discrimination (54.2%). Approximately 83% of respondents believed that parental consent should be required to screen newborns for LFS. Conclusion: This study revealed strong support for NBS for LFS despite the recognition of various perceived benefits and risks. These findings underscore the complex interplay between clinical, psychosocial, and ethical factors in considering NBS for LFS from the perspective of the LFS community.

Material financial hardship and insurance-related experiences among Utah's rural and urban cancer survivors.

PURPOSE: Describe material financial hardship (e.g., using savings, credit card debt), insurance, and access to care experienced by Utah cancer survivors; investigate urban-rural differences in financial hardship. METHODS: Cancer survivors were surveyed from 2018 to 2021 about their experiences with financial hardship, access to healthcare, and job lock (insurance preventing employment changes). Weighed percentage responses, univariable and multivariable logistic regression models for these outcomes compared differences in survivors living in rural and urban areas based on Rural-Urban Commuting Area Codes. RESULTS: The N = 1793 participants were predominantly Non-Hispanic White, female, and 65 or older at time of survey. More urban than rural survivors had a college degree (39.8% vs. 31.0%, p = 0.04). Overall, 35% of survivors experienced ≥ 1 financial hardship. In adjusted analyses, no differences were observed between urban and rural survivors for: material financial hardship, the overall amount of hardship reported, insurance status at survey, access to healthcare, or job lock. Hispanic rural survivors were less likely to report financial hardship than Hispanic urban survivors (odds ratio (OR) = 0.24, 95%CI = 0.08-0.73)). Rural survivors who received chemo/immune therapy as their only treatment were more likely to report at least one instance of financial hardship than urban survivors (OR = 2.72, 95%CI = 1.08-6.86). CONCLUSIONS: The relationship between rurality and financial hardship among survivors may be most burdensome for patients whose treatments require travel or specialty medication access. IMPLICATIONS FOR CANCER SURVIVORS: The impact of living rurally on financial difficulties after cancer diagnoses is complex. Features of rurality that may alter financial difficulty after a cancer diagnosis may vary geographically and instead of considering rurality as a stand-alone factor, these features should be investigated independently.

Accuracy of patient race and ethnicity data in a central cancer registry.

PURPOSE: Race and Hispanic ethnicity data can be challenging for central cancer registries to collect. We evaluated the accuracy of the race and Hispanic ethnicity variables collected by the Utah Cancer Registry compared to self-report. METHODS: Participants were 3,162 cancer survivors who completed questionnaires administered in 2015-2022 by the Utah Cancer Registry. Each survey included separate questions collecting race and Hispanic ethnicity, respectively. Registry-collected race and Hispanic ethnicity were compared to self-reported values for the same individuals. We calculated sensitivity and specificity for each race category and Hispanic ethnicity separately. RESULTS: Survey participants included 323 (10.2%) survivors identifying as Hispanic, a lower proportion Hispanic than the 12.1% in the registry Hispanic variable (sensitivity 88.2%, specificity 96.5%). For race, 43 participants (1.4%) self-identified as American Indian or Alaska Native (AIAN), 32 (1.0%) as Asian, 23 (0.7%) as Black or African American, 16 (0.5%) Pacific Islander (PI), and 2994 (94.7%) as White. The registry race variable classified a smaller proportion of survivors as members of each of these race groups except White. Sensitivity for classification of race as AIAN was 9.3%, Asian 40.6%, Black 60.9%, PI 25.0%, and specificity for each of these groups was > 99%. Sensitivity and specificity for White were 98.8% and 47.4%. CONCLUSION: Cancer registry race and Hispanic ethnicity data often did not match the individual's self-identification. Of particular concern is the high proportion of AIAN individuals whose race is misclassified. Continued attention should be directed to the accurate capture of race and ethnicity data by hospitals.

Characteristics of pediatric patients with multiple sclerosis and related disorders infected with SARS-CoV-2.

BACKGROUND: Pediatric patients with multiple sclerosis (POMS) and related disorders, clinically isolated syndrome (CIS), myelin oligodendrocyte glycoprotein antibody disorder (MOGAD), and neuromyelitis optica spectrum disorder (NMOSD), are commonly treated with immunosuppressants. Understanding the impact of SARS-CoV-2 infection in patients may inform treatment decisions. OBJECTIVE: Characterize SARS-CoV-2 infection prevalence and severity among a cohort of patients with POMS and related disorders, as well as the impact of disease-modifying therapies (DMTs). METHODS: POMS and related disorders patients enrolled in a large, prospective registry were screened for COVID-19 during standard-of-care neurology visits. If confirmed positive of having infection, further analysis was undertaken. RESULTS: Six hundred and sixty-nine patients were surveyed between March 2020 and August 2021. There were 73 confirmed COVID-19 infections. Eight of nine hospitalized patients (89%), and all patients admitted to the ICU were treated with B cell depleting therapy. The unadjusted odds ratio of hospitalization among those who tested positive of having had COVID-19 was 15.27 among those on B-cell-depleting therapy (p = 0.016). CONCLUSIONS: B-cell-depleting treatment was associated with a higher risk of COVID-19, higher rates of hospitalization, and ICU admission, suggesting this therapy carries a higher risk of severe infection in POMS and related disorders.

Cancer survivorship experiences in Utah: an evaluation assessing indicators of survivors' quality of life, health behaviors, and access to health services.

PURPOSE: The 2016-2020 Utah Comprehensive Cancer Prevention and Control Plan prioritized strategies to address cancer survivorship experiences. In this paper we present estimates for nine indicators evaluating these priorities, trends over time, and assess disparities in survivorship experiences across demographic subgroups. METHODS: We surveyed a representative sample of Utah cancer survivors diagnosed between 2012 and 2019 with any reportable cancer diagnosis. We calculated weighted percentages and 95% confidence intervals (CI) for each indicator. We assessed change over time using a test for trend across survey years in a logistic regression model and used Rao-Scott F-adjusted chi-square tests to test the association between demographic characteristics and each survivorship indicator. RESULTS: Most of the 1,793 respondents (93.5%) reported their pain was under control, 85.7% rated their overall health as good, very good, or excellent, but 46.5% experienced physical, mental, or emotional limitations. Only 1.7% of survivors aged 75 or older were current smokers, compared to 5.8% of 65-74-year-olds and 7.9% of survivors aged 55-74 (p < 0.006). No regular physical activity was reported by 20.6% and varied by survivor age and education level. The proportion who received a survivorship care plan increased from 34.6% in 2018 to 43.0% in 2021 (p = 0.025). However, survivors under age 55 were significantly less likely to receive a care plan than older survivors. CONCLUSION: This representative survey of cancer survivors fills a gap in understanding of the cancer survivorship experience in Utah. Results can be used to evaluate and plan additional interventions to improve survivorship quality of life.

MOG and AQP4 Antibodies among Children with Multiple Sclerosis and Controls.

OBJECTIVE: The purpose of this study was to determine the frequency of myelin oligodendrocyte glycoprotein (MOG)-IgG and aquaporin-4 (AQP4)-IgG among patients with pediatric-onset multiple sclerosis (POMS) and healthy controls, to determine whether seropositive cases fulfilled their respective diagnostic criteria, to compare characteristics and outcomes in children with POMS versus MOG-IgG-associated disease (MOGAD), and identify clinical features associated with final diagnosis. METHODS: Patients with POMS and healthy controls were enrolled at 14 US sites through a prospective case-control study on POMS risk factors. Serum AQP4-IgG and MOG-IgG were assessed using live cell-based assays. RESULTS: AQP4-IgG was negative among all 1,196 participants, 493 with POMS and 703 healthy controls. MOG-IgG was positive in 30 of 493 cases (6%) and zero controls. Twenty-five of 30 patients positive with MOG-IgG (83%) had MOGAD, whereas 5 of 30 (17%) maintained a diagnosis of multiple sclerosis (MS) on re-review of records. MOGAD cases were more commonly in female patients (21/25 [84%] vs 301/468 [64%]; p = 0.044), younger age (mean = 8.2 ± 4.2 vs 14.7 ± 2.6 years; p < 0.001), more commonly had initial optic nerve symptoms (16/25 [64%] vs 129/391 [33%]; p = 0.002), or acute disseminated encephalomyelitis (ADEM; 8/25 [32%] vs 9/468 [2%]; p < 0.001), and less commonly had initial spinal cord symptoms (3/20 [15%] vs 194/381 [51%]; p = 0.002), serum Epstein-Barr virus (EBV) positivity (11/25 [44%] vs 445/468 [95%]; p < 0.001), or cerebrospinal fluid oligoclonal bands (5/25 [20%] vs 243/352 [69%]; p < 0.001). INTERPRETATION: MOG-IgG and AQP4-IgG were not identified among healthy controls confirming their high specificity for pediatric central nervous system (CNS) demyelinating disease. Five percent of those with prior POMS diagnoses ultimately had MOGAD; and none had AQP4-IgG positivity. Clinical features associated with a final diagnosis of MOGAD in those with suspected MS included initial ADEM phenotype, younger age at disease onset, and lack of EBV exposure. ANN NEUROL 2023;93:271-284.

Age-based variability in the association between restraint use and injury type and severity in multi-occupant crashes.

PURPOSE: Previous studies have shown older adults receive relatively less protection from seat belts against fatal injuries, however it is unknown how seat belt protection against severe and torso injury changes with age. We estimated age-based variability in seat belt protection against fatal injuries, injuries with maximum abbreviated injury scale greater than two (MAIS 3+), and torso injuries. METHODS: We leveraged the Crash Outcome Data Evaluation System to analyze binary indicators of fatal, MAIS 3+, and torso injuries. Using a matched cohort design and conditional Poisson regression, we estimated age-based relative risks (RR) of the outcomes associated with seat belt use. RESULTS: Our results suggested that seat belts were highly protective against fatal injuries for all ages. For ages 16-30, seat belt use was associated with 66% lower risk of MAIS3+ injury (RR 0.34, 95% CI 0.30, 0.38) for occupants of the same vehicle, whereas for ages 75 and older, seat belt use was associated with 38% lower risk of MAIS3+ injury (RR 0.62; 95% CI 0.45, 0.86) for occupants in the same vehicle. The association between restraint use and torso injury also attenuated with age. CONCLUSIONS: In multi-occupant crashes, seat belts were highly protective against fatal and MAIS3+ injury, however seat belt protection against MAIS3+ and torso injury attenuated with age.

Socioeconomic and Demographic Factors Effect in Association with Driver's Medical Services after Crashes.

Motor vehicle crashes are the third leading cause of preventable-injury deaths in the United States. Previous research has found links between the socioeconomic characteristics of driver residence zip codes and crash frequencies. The objective of the study is to extend earlier work by investigating whether the socioeconomic characteristics of a driver's residence zip code influence their likelihood of resulting in post-crash medical services. Data were drawn from General Use Model (GUM) data for police crash reports linked to hospital records in Kentucky, Utah, and Ohio. Zip-code-level socioeconomic data from the American Community Survey were also incorporated into analyses. Logistic regression models were developed for each state and showed that the socioeconomic variables such as educational attainment, median housing value, gender, and age have p-values < 0.001 when tested against the odds of seeking post-crash medical services. Models for Kentucky and Utah also include the employment-to-population ratio. The results show that in addition to age and gender, educational attainment, median housing value and rurality percentage at the zip code level are associated with the likelihood of a driver seeking follow-up medical services after a crash. It is concluded that drivers from areas with lower household income and lower educational attainment are more likely to seek post-crash medical services, primarily in emergency departments. Female drivers are also more likely to seek post-crash medical services.

Ready for Children Part II: Increasing Pediatric Care Coordination and Psychomotor Skills Evaluation in the Prehospital Setting.

Objectives: Treating pediatric patients often invokes discomfort and anxiety among emergency medical service (EMS) personnel. As part of the process to improve pediatric care in the prehospital system, the Health Resources and Services Administration (HRSA) Emergency Services for Children (EMSC) Program implemented two prehospital performance measures -access to a designated pediatric care coordinator (PECC) and skill evaluation using pediatric equipment-along with a multi-year plan to aid states in achieving the measures. Baseline data from a survey conducted in 2017 showed that less than 25% of EMS agencies had access to PECC and 47% performed skills evaluation using pediatric equipment at least twice a year. To evaluate change over time, the survey was again conducted in 2020, and agencies that participated in both years are compared. Methods: A web-based survey was sent to EMS agency administrators in 58 states and territories from January to March 2020. Descriptive statistics, odds ratios, and 95% confidence intervals were conducted. Results: The response rate was 56%. A total of 5,221 agencies participated in both survey periods representing over 250,000 providers. The percentage of agencies reporting the presence of a PECC increased from 24% to 34% (p= <0.001). However, some agencies reported that they no longer had a PECC, while others reported having a PECC for the first time. Fifty percent (50%) of agencies conduct pediatric psychomotor skills evaluation at least twice/year, a 2% increase over time (p = 0.041); however, a third (34%) evaluate skills using pediatric equipment less than once a year. The presence of a PECC continues to be the variable associated with the highest odds (AOR 2.15, 95% CI 1.91-2.43) of conducting at least semiannual skills evaluation.Conclusions: There is an increase in the presence of pediatric care coordination and the frequency of pediatric psychomotor skills evaluation among national EMS agencies over time. Continued efforts to increase and sustain PECC presence should be an ongoing focus to improve pediatric readiness in the prehospital system.

Increased Prevalence of Familial Autoimmune Disease in Children With Opsoclonus-Myoclonus Syndrome.

BACKGROUND AND OBJECTIVES: Opsoclonus-myoclonus syndrome (OMS) is a rare autoimmune disorder associated with neuroblastoma in children, although idiopathic and postinfectious etiologies are present in children and adults. Small cohort studies in homogenous populations have revealed elevated rates of autoimmunity in family members of patients with OMS, although no differentiation between paraneoplastic and nonparaneoplastic forms has been performed. The objective of this study was to investigate the prevalence of autoimmune disease in first-degree relatives of pediatric patients with paraneoplastic and nonparaneoplastic OMS. METHODS: A single-center cohort study of consecutively evaluated children with OMS was performed. Parents of patients were prospectively administered surveys on familial autoimmune disease. Rates of autoimmune disease in first-degree relatives of pediatric patients with OMS were compared using Fisher exact t test and χ2 analysis: (1) between those with and without a paraneoplastic cause and (2) between healthy and disease (pediatric multiple sclerosis [MS]) controls from the United States Pediatric MS Network. RESULTS: Thirty-five patients (18 paraneoplastic, median age at onset 19.0 months; 17 idiopathic, median age at onset 25.0 months) and 68 first-degree relatives (median age 41.9 years) were enrolled. One patient developed systemic lupus erythematosus 7 years after OMS onset. Paraneoplastic OMS was associated with a 50% rate of autoimmune disease in a first-degree relative compared with 29% in idiopathic OMS (p = 0.31). The rate of first-degree relative autoimmune disease per OMS case (14/35, 40%) was higher than healthy controls (86/709, 12%; p < 0.001) and children with pediatric MS (101/495, 20%; p = 0.007). DISCUSSION: In a cohort of pediatric patients with OMS, there were elevated rates of first-degree relative autoimmune disease, with no difference in rates observed between paraneoplastic and idiopathic etiologies, suggesting an autoimmune genetic contribution to the development of OMS in children.