Pandemics are inherently disruptive, evoking uncomfortable and unsustainable emotions. We explore the emotional landscape of the COVID-19 pandemic and its normalization among vaccine hesitant residents in Oklahoma. Ontological insecurity reported at the pandemic's outset stemmed from the absence of a clear and resonant cultural script that left individuals to construct narratives in which COVID-19 came to be understood as the "New Flu." Within a backdrop of institutional distrust, participants enacted this narrative through individual health practices. The "New Flu" became a symbol that normalized ontological disruption by transforming the perception of COVID-19 as uncertain and existentially threatening into emotionally manageable.

BACKGROUND:Epidemiologic studies have demonstrated associations between congenital heart disease (CHD) and childhood cancer. However, these assessments have not fully accounted for the pathogenetic and clinical heterogeneity of CHD, limiting their capacity to inform pathogenetic studies and the clinical management of children with CHD. METHODS:To achieve a more detailed understanding of cancer risk in children with nonsyndromic CHD, we evaluated 60 cardiac lesions in 7 categories in a cohort of 11 million children from Massachusetts, North Carolina, Oklahoma, and Texas. We used Cox proportional hazards regression to estimate the hazard ratios (HRs) and 95% CIs of cancer in children with each lesion relative to children without congenital anomalies when there were ≥3 co-occurring cases. RESULTS:We identified 74 755 children with CHD and observed increased hazards for several malignancies. Notable associations included aortic arch obstruction-lymphoma (HR, 12.7 [95% CI, 4.9-31.0]); single-ventricle disease-lymphoma (HR, 9.7 [95% CI, 3.8-24.4]); complex atrioventricular septal defect-leukemia (HR, 8.05 [95% CI, 2.8-23.0]); ventricular septal defect-hepatoblastoma (HR, 11.2 [95% CI, 5.9-21.1]); and conotruncal defects-neuroblastoma (HR, 6.4 [95% CI, 1.9-22.2]). The cumulative incidence of cancer was <1% for all CHD groups evaluated. CONCLUSIONS:Cancer incidence in children with nonsyndromic CHD was generally low. However, we identified >5-fold increases in the hazard of hepatoblastoma, neuroblastoma, leukemia, and lymphoma in children with certain lesions. Our findings may assist in generating hypotheses about the causes of cancer in children with CHD.

BACKGROUND:Pediatric sarcomas are a heterogeneous group of tumors that contribute disproportionately to cancer mortality in children. Although congenital anomalies are among the strongest known risk factors for childhood cancer, the risk of specific sarcoma subtypes among affected individuals has not yet been thoroughly evaluated. PROCEDURE:We obtained data on maternal and perinatal characteristics, congenital anomalies, and pediatric sarcoma diagnoses for all live births in nine states. We used Cox proportional hazards regression to estimate the hazard ratio (HR) and 95% confidence interval (CI) of sarcoma (overall and by subtype) among children with non-syndromic congenital anomalies. We considered all non-syndromic anomalies collectively, and when sample size allowed, we also evaluated specific anomaly-sarcoma associations. RESULTS:We evaluated 21,933,884 children, including 641,770 (2.9%) with major non-syndromic congenital anomalies. Compared to children without a congenital anomaly, children with a non-syndromic anomaly had a two-fold higher hazard for any soft tissue sarcoma (95% CI: 1.7-2.5), including rhabdomyosarcoma (HR 2.2, 95% CI: 1.7-3.0) and embryonal rhabdomyosarcoma (HR 2.5, 95% CI: 1.8-3.6), as well as non-rhabdomyosarcoma soft tissue sarcoma (HR 1.8, 95% CI: 1.3-2.5). The hazard of embryonal rhabdomyosarcoma was markedly increased in children with central nervous system anomalies (HR 7.9, 95% CI: 3.9-15.9), obstructive genitourinary defects (HR 4.6, 95% CI: 2.2-9.7), and limb reduction deformities (HR 3.8, 95% CI: 1.6-9.3). CONCLUSIONS:Children with non-syndromic congenital anomalies are at increased risk of sarcomas, especially soft tissue sarcomas. Future studies should clarify shared developmental pathways and evaluate implications for sarcoma risk prediction and surveillance.

INTRODUCTION:American Indian/Alaska Native (AI/AN) individuals were disproportionately affected by the COVID-19 pandemic. We aimed to evaluate whether the presence of chronic health conditions (CHC) impacted COVID-19 testing and vaccination for AI/AN people in Oklahoma. METHODS:We pooled survey data that included adult AI/AN participants weighted using the 2022 American Community Survey. We used modified Poisson regression to estimate prevalence proportion ratios (PPR) and 95% confidence intervals (CI) accounting for weighting, multiple imputation, and confounders to determine whether access to COVID-19 testing and vaccine uptake differed by CHC status. RESULTS:Among the 1,139 participants, 62.6% reported being diagnosed with a CHC. The majority reported being tested for COVID-19 (80.6%) and that testing access was easy (81.7%). We observed no association between CHCs and being tested (Adjusted PPR: 1.08, 95% CI: 0.97, 1.19) or testing access (Adjusted PPR: 1.08, 95% CI: 0.95, 1.21). Over half (57%) of participants received a COVID-19 vaccine. Among unvaccinated individuals, 9.7% reported they were likely to get a vaccine. While we observed no association between CHCs and vaccine status (Adjusted PPR: 1.08, 95% CI: 0.90, 1.27), unvaccinated individuals with a CHC reported they were more likely to get a vaccine compared to individuals with no CHC (Adjusted PPR: 1.81, 95% CI: 1.01, 2.62). DISCUSSION:The AI/AN population is at higher risk of developing CHC, which increases the risk for severe COVID-19. Thus, evaluating barriers to accessing testing and vaccines is important to improve outcomes. This analysis is important in supporting programs for seasonal epidemics and future pandemics. TRIAL REGISTRATION NUMBERS:NCT04870307, NCT05236270.

Evidence describing paediatric COVID-19 and influenza co-infection is limited because influenza circulation was minimal during the early COVID-19 pandemic. We used the National Clinical Cohort Collaborative, a multicentre electronic health record repository, to describe the characteristics and clinical outcomes of paediatric COVID-19 and influenza co-infections in the United States from March 2020-April 2024. We defined co-infection as COVID-19 and influenza identified <7 days apart. We reported demographics, pre-existing diagnoses, and clinical outcomes and used generalized estimating equation models. We defined clinical outcomes as Severe/Moderate disease (hospitalization, critical care, or death) versus emergency department/outpatient encounters. We repeated analyses using varying co-infection definitions to assess robustness of findings. Among 1.53 million patients, 10,277 were co-infected, and 647 (6%) were hospitalized. Co-infections occurred predominantly among children aged <12 years. The most common pre-existing diagnoses were obesity (24%), asthma (10%), and congenital/genetic conditions (5%). The risk for Severe/Moderate disease was greatest among persons aged 0-4 years (adjusted risk ratio (aRR) 3.05; 95% confidence interval (CI): 2.35-3.97) and those with ≥2 pre-existing diagnoses (aRR 2.89; 95% CI: 2.43-3.43). Similar distributions of disease severity were observed across varying co-infection definitions. This study provides a large-scale epidemiological characterization of paediatric COVID-19 and influenza co-infection and successfully implemented a practical EHR-based co-infection case definition for future analyses.

Supplementary Figure S1: Directed acyclic graph guiding confounder selection.

BACKGROUND:Congenital anomalies are associated with an increased risk of childhood cancer. However, there is a knowledge gap about health outcomes for childhood cancer survivors with congenital anomalies. METHODS:We included childhood cancer survivors from the Childhood Cancer Survivor Study (n = 22,247), comparing survivors with and without self-reported anomalies. Using Cox regression, we estimated HR and 95% confidence intervals (CI) of chronic health conditions (CHC) classified per the Common Terminology Criteria for Adverse Events from 1 (mild) to 5 (fatal) and subsequent malignant neoplasms (SMN), comparing survivors by anomaly status. We calculated age-, sex-, and calendar year-specific mortality rates and standardized mortality ratios for survivors compared with the US population. RESULTS:Among survivors, 16.9% (n = 3,880) reported a congenital anomaly. Survivors with anomalies had a higher rate of any CHC (grades 1-5: HR, 1.24; 95% CI, 1.18-1.31), severe CHCs (grades 3-5: HR, 1.29; 95% CI, 1.19-1.40), and multiple CHCs of any grade (≥2 CHCs: HR, 1.31; 95% CI, 1.24-1.39; ≥3 CHCs: HR, 1.42; 95% CI, 1.33-1.52). Survivors with anomalies had an increased rate of soft-tissue sarcomas (HR, 1.96; 95% CI, 1.12-3.44). For deaths related to the original cancer diagnosis, survivors with anomalies (compared with those with no anomalies) had a lower mortality rate (0.64 vs. 0.90 per 1,000 person-years). CONCLUSIONS:We identified an increased rate of CHCs and SMNs among childhood cancer survivors with anomalies and lower mortality directly related to the cancer diagnosis. IMPACT:Future work will focus on the evaluation of genetic pathways that increase the risk of CHCs and SMNs.

Cancer risk in children with VACTERL, a nonrandom co-occurrence of ≥ 3 defects (vertebral, anal, cardiac, tracheoesophogeal fistula, renal, and limb), remains unclear. We evaluated this association in a population-based study. We analyzed data from the Genetic Overlap Between Anomalies and Cancer in Kids (GOBACK) Study, a US registry linkage cohort. VACTERL was defined as the presence of ≥ 3 associated defects. Cox regression was applied to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for cancer risk before age 18 in children with VACTERL compared to children without birth defects. Kaplan-Meier analyses were used to estimate cumulative incidence of cancer in each group. Of 21,224,742 births, 2288 met VACTERL criteria; 8 developed cancer, 5 (63%) of whom were diagnosed with embryonal tumors. Children with VACTERL had a significantly increased cancer risk (HR = 3.0, 95% CI: 1.5-6.0), particularly for embryonal tumors (HR = 6.9, 95% CI: 2.9-16.5), relative to unaffected children. Cancer incidence was 421.3 (95% CI: 181.9, 830.0) per million person-years for VACTERL versus 133.4 (95% CI: 131.8-135.0) for unaffected children. Children with VACTERL may face increased cancer risk. Shared developmental or epigenetic mechanisms may underlie both conditions, highlighting efforts to identify subgroups that may benefit from targeted surveillance.

BACKGROUND:Children born with a congenital anomaly have a higher risk of developing a brain tumor during childhood or adolescence, but the co-occurrence between specific types of congenital anomalies and specific types of childhood brain tumors (CBTs) is not well described. This study characterized the associations between specific congenital anomalies and CBTs. METHODS:We leveraged a population-based registry linkage study of births (1990-2018), congenital anomalies, and cancer from 9 states (n = 22,599,099 births). Congenital anomalies were classified as major structural without a known chromosomal or genetic syndrome, chromosomal, neurofibromatosis, and/or tuberous sclerosis complex. CBT classification was based on the International Classification of Childhood Cancer for children diagnosed < 20 years. Cox regression analyses were conducted separately by congenital anomaly for anomaly-CBT combinations with at least 5 co-occurring cases. We conducted analyses for any CBT and separately for astrocytoma, atypical teratoid/rhabdoid tumor, ependymoma, medulloblastoma, mixed and unspecified gliomas, and primitive neuroectodermal tumors. RESULTS:There were 6,247 children diagnosed with a CBT. Having any major structural anomaly was associated with risk of any CBT and across all subgroups (aHR range: 1.48-3.69) except ependymoma, particularly among children diagnosed with a tumor by 1 year of age. Of the 66 anomaly-CBT combinations analyzed, 42 were significant (P < .05), including 25 in an earlier version of this study and 16 novel associations (aHR range: 1.46-525). Anomaly-CBT associations also differed by astrocytoma histology. CONCLUSIONS:We observed consistent evidence that having a structural congenital anomaly increases risk of developing a CBT, particularly in infancy, which may provide insights into etiology.

BACKGROUND:Birth defects are associated with childhood cancer, but little is known regarding pediatric carcinomas, a group of especially rare tumors. METHODS:We used Cox proportional hazards regression to estimate the hazard ratio (HR) and 95 % confidence interval (CI) for any carcinoma, as well as thyroid, hepatocellular, and renal carcinoma specifically, up to 18 years of age among children with major, non-syndromic anomalies or chromosomal/genetic syndromes, relative to unaffected children. RESULTS:Our registry-linkage study included nine states and 21,933,476 children between 1990 and 2018: 641,827 with non-syndromic anomalies, and 49,619 with syndromes. Carcinomas were diagnosed in 833 children, including 35 with non-syndromic anomalies and eight with syndromes. The hazard of carcinoma was increased both among children with non-syndromic anomalies (HR: 1.7, CI: 1.2-2.4; N = 35) and syndromes (HR: 4.7, CI: 2.3-9.5; N = 7). Hepatocellular carcinoma was associated with non-syndromic anomalies (HR: 4.6, CI: 2.2-9.7; N = 8) and syndromes (HR: 8.0, CI: 1.1-58.1; N < 5). The hazard of renal carcinoma was markedly increased in children with tuberous sclerosis (HR 59.6, CI: 23.7-149.5; N = 5), a known cause of renal cancer. Thyroid carcinoma was not associated with non-syndromic anomalies or syndromes. CONCLUSION:Birth defects are associated with hepatocellular and renal carcinoma in children.

Supplementary Table S4: Rate of chronic health conditions by number of anomalies.

Directed acyclic graph of the potential associations between rurality at time of diagnosis and survivors with Passport for Care

Birth defects are associated with increased cancer risk in the general pediatric population, yet their impact on leukemia risk in children with Down syndrome (DS) remains uncertain. We assessed this using data from 26,660 children with DS in the Genetic Overlap Between Anomalies and Cancer in Kids Registry Linkage Study. Among them, 71.9

Supplementary Table S2: Rate of specific chronic health conditions by anomaly status.

Supplementary Figure S3: Cumulative mortality by cause of death

OBJECTIVE:Calibration and discrimination indicators alone are insufficient for evaluating the clinical usefulness of prediction models, as they do not account for the cost of misclassification errors. This study aimed to modify the Geriatric Trauma Outcome Score (GTOS) and assess the clinical utility of the modified model using net benefit (NB) and decision curve analysis (DCA) for predicting in-hospital mortality. METHODS:The Trauma Quality Improvement Program (TQIP) 2017 was used to identify geriatric trauma patients (≥ 65 years) treated at Level I trauma centers. The outcome of interest was in-hospital mortality. The GTOS was modified to include additional patient, injury, and treatment characteristics identified through machine learning methods, focusing on early risk stratification. Calibration and discrimination indicators, along with NB and DCA, were utilized for evaluation. RESULTS:Of the 67,222 admitted geriatric trauma patients, 5.6% died in the hospital. The modified GTOS score included the following variables with associated weights: initial airway intervention (5), Glasgow Coma Scale ≤13 (5), packed red blood cell transfusion within 24 h (3), penetrating injury (2), age ≥ 75 years (2), preexisting comorbidity (1), and torso injury (1), with a total range from 0 to 19. The modified GTOS demonstrated a significantly higher area under the curve (0.92 vs. 0.84, p < 0.0001), lower misclassification error (4.9% vs. 5.2%), and lower Brier score (0.036 vs. 0.042) compared to the original GTOS. DCA showed that using the modified GTOS for predicting in-hospital mortality resulted in higher NB than treating all, treating none, and treating based on the original GTOS across a wide range of clinician preferences. CONCLUSIONS:The modified GTOS model exhibited superior predictive ability and clinical utility compared to the original GTOS. NB and DCA offer valuable complementary methods to calibration and discrimination indicators, comprehensively evaluating the clinical usefulness of prediction models and decision strategies.