Mortality follow-up of Fernald Feed Materials Production Center workers exposed to uranium from 1951 to 1985.

OBJECTIVE: This follow-up study of uranium processing workers at the Fernald Feed Materials Production Center examines the relationship between radiation exposure and cancer and non-cancer mortality among 6403 workers employed for at least 30 days between 1951 and 1985. METHODS: We estimated cumulative, individual, annualised doses to 15 organs/tissues from external, internal and radon exposures. Vital status and cause of death were ascertained in 2017. The analysis employed standardised mortality ratios, Cox proportional hazards and Poisson regression models. Competing risk analysis was conducted for cardiovascular disease (CVD) mortality risk given several assumptions about risk independent of competing outcomes. Emphysema was examined to assess the potential for confounding by smoking. RESULTS: Vital status was confirmed for 98.1% of workers, with 65.1% deceased. All-cause mortality was less than expected in salaried but not hourly workers when compared with the US population. A statistically significant dose response was observed between external (but not total or internal) lung dose and lung cancer mortality (HR at 100 mGy adjusted for internal dose=1.45; 95% CI=1.05 to 2.01). Significantly increased HRs at 100 mGy dose to heart were observed for CVD (1.27; 95% CI=1.07 to 1.50) and ischaemic heart disease (1.30; 95% CI=1.07 to 1.58). CVD risk remained elevated regardless of competing risk assumptions. Both external and internal radiation were associated with emphysema. CONCLUSIONS: Lung cancer was associated with external dose, though positive dose responses for emphysema imply residual confounding by smoking. Novel use of competing risk analysis for CVD demonstrates leveraging retrospective data for future risk prediction.

Recommendations on statistical approaches to account for dose uncertainties in radiation epidemiologic risk models.

PURPOSE: Epidemiological studies of stochastic radiation health effects such as cancer, meant to estimate risks of the adverse effects as a function of radiation dose, depend largely on estimates of the radiation doses received by the exposed group under study. Those estimates are based on dosimetry that always has uncertainty, which often can be quite substantial. Studies that do not incorporate statistical methods to correct for dosimetric uncertainty may produce biased estimates of risk and incorrect confidence bounds on those estimates. This paper reviews commonly used statistical methods to correct radiation risk regressions for dosimetric uncertainty, with emphasis on some newer methods. We begin by describing the types of dose uncertainty that may occur, including those in which an uncertain value is shared by part or all of a cohort, and then demonstrate how these sources of uncertainty arise in radiation dosimetry. We briefly describe the effects of different types of dosimetric uncertainty on risk estimates, followed by a description of each method of adjusting for the uncertainty. CONCLUSIONS: Each of the method has strengths and weaknesses, and some methods have limited applicability. We describe the types of uncertainty to which each method can be applied and its pros and cons. Finally, we provide summary recommendations and touch briefly on suggestions for further research.

A Historical Survey of Key Epidemiological Studies of Ionizing Radiation Exposure.

In this article we review the history of key epidemiological studies of populations exposed to ionizing radiation. We highlight historical and recent findings regarding radiation-associated risks for incidence and mortality of cancer and non-cancer outcomes with emphasis on study design and methods of exposure assessment and dose estimation along with brief consideration of sources of bias for a few of the more important studies. We examine the findings from the epidemiological studies of the Japanese atomic bomb survivors, persons exposed to radiation for diagnostic or therapeutic purposes, those exposed to environmental sources including Chornobyl and other reactor accidents, and occupationally exposed cohorts. We also summarize results of pooled studies. These summaries are necessarily brief, but we provide references to more detailed information. We discuss possible future directions of study, to include assessment of susceptible populations, and possible new populations, data sources, study designs and methods of analysis.

Factors Affecting Specialty Training Preference Among UK Medical Students (FAST): Protocol for a National Cross-Sectional Survey.

BACKGROUND: The UK medical education system faces a complex landscape of specialty training choices and heightened competition. The Factors Affecting Specialty Training Preference Among UK Medical Students (FAST) study addresses the need to understand the factors influencing UK medical students' specialty choices, against a backdrop of increasing challenges in health care workforce planning. OBJECTIVE: The primary objectives of the FAST study are to explore UK medical students' preferred specialties and the factors that influence these choices. Secondary objectives are to evaluate students' confidence in securing their chosen specialty, to understand how demographic and academic backgrounds affect their decisions, and to examine how specialty preferences and confidence levels vary across different UK medical schools. METHODS: A cross-sectional survey design will be used to collect data from UK medical students. The survey, comprising 17 questions, uses Likert scales, multiple-choice formats, and free-text entry to capture nuanced insights into specialty choice factors. The methodology, adapted from the Ascertaining the Career Intentions of UK Medical Students (AIMS) study, incorporates adjustments based on literature review, clinical staff feedback, and pilot group insights. This approach ensures comprehensive and nondirective questioning. Data analysis will include descriptive statistics to establish basic patterns, ANOVA for group comparisons, logistic regression for outcome modeling, and discrete choice models for specialty preference analysis. RESULTS: The study was launched nationally on December 4, 2023. Data collection is anticipated to end on March 1, 2024, with data analysis beginning thereafter. The results are expected to be available later in 2024. CONCLUSIONS: The FAST study represents an important step in understanding the factors influencing UK medical students' career pathways. By integrating diverse student perspectives across year groups and medical schools, this study seeks to provide critical insights into the dynamics of specialty, or residency, selection. The findings are anticipated to inform both policy and educational strategies, aiming to align training opportunities with the evolving needs and aspirations of the future medical workforce. Ultimately, the insights gained may guide initiatives to balance specialty distribution, improve career guidance, and improve overall student satisfaction within the National Health Service, contributing to a more stable and effective health care system. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/55155.

Bayesian transition models for ordinal longitudinal outcomes.

Ordinal longitudinal outcomes are becoming common in clinical research, particularly in the context of COVID-19 clinical trials. These outcomes are information-rich and can increase the statistical efficiency of a study when analyzed in a principled manner. We present Bayesian ordinal transition models as a flexible modeling framework to analyze ordinal longitudinal outcomes. We develop the theory from first principles and provide an application using data from the Adaptive COVID-19 Treatment Trial (ACTT-1) with code examples in R. We advocate that researchers use ordinal transition models to analyze ordinal longitudinal outcomes when appropriate alongside standard methods such as time-to-event modeling.

A real-time prognostic model for venous thromboembolic events among hospitalized adults.

Background: Hospital-acquired venous thromboembolism (HA-VTE) is a leading cause of morbidity and mortality among hospitalized adults. Guidelines recommend use of a risk-prediction model to estimate HA-VTE risk for individual patients. Extant models do not perform well for broad patient populations and are not conducive to automation in clinical practice. Objectives: To develop an automated, real-time prognostic model for venous thromboembolism during hospitalization among all adult inpatients using readily available data from the electronic health record. Methods: The derivation cohort included inpatient hospitalizations ("encounters") for patients ≥16 years old at Vanderbilt University Medical Center between 2018 and 2020 (n = 132,330). HA-VTE events were identified using International Classification of Diseases, 10th Revision, codes. The prognostic model was developed using least absolute shrinkage and selection operator regression. Temporal external validation was performed in a validation cohort of encounters between 2021 and 2022 (n = 62,546). Prediction performance was assessed by discrimination accuracy (C statistic) and calibration (integrated calibration index). Results: There were 1187 HA-VTEs in the derivation cohort (9.0 per 1000 encounters) and 864 in the validation cohort (13.8 per 1000 encounters). The prognostic model included 25 variables, with placement of a central line among the most important predictors. Prediction performance of the model was excellent (C statistic, 0.891; 95% CI, 0.882-0.900; integrated calibration index, 0.001). The model performed similarly well across subgroups of patients defined by age, sex, race, and type of admission. Conclusion: This fully automated prognostic model uses readily available data from the electronic health record, exhibits superior prediction performance compared with existing models, and generates granular risk stratification in the form of a predicted probability of HA-VTE for each patient.

Adjustment for duration of employment in occupational epidemiology.

PURPOSE: In occupational epidemiology, the healthy worker survivor effect can manifest as a time-dependent confounder because healthier workers can accrue greater amounts of exposure over longer periods of employment. For example, in occupational studies of radiation exposure that focus on cumulative annualized radiation dose, workers can accrue greater amounts of cumulative radiation exposure over longer periods of employment, while workers with longer periods of employment can transition into jobs with a reduced potential for annualized radiation exposure. The extent to which confounding arising from the healthy worker survivor effect impacts radiation risk estimates is unknown. METHODS: We assessed the impact of the healthy worker survivor effect on estimates of radiation risk among nuclear workers in a Million Person Study cohort. In simulation studies, we contrasted the ability of marginal structural Cox models with inverse probability weighting and Cox proportional hazards models to account for time-dependent confounding arising from the healthy worker survivor effect. RESULTS: Marginal structural Cox models and Cox proportional hazards models with flexible functional forms for duration of employment provided reliable results. CONCLUSIONS: It is crucial to flexibly adjust for duration of employment to account for confounding arising from the healthy worker survivor effect in occupational epidemiology.

Are Formal and Informal Home Mindfulness Practice Quantities Associated With Outcomes? Results From a Pilot Study of a Four-Week Mindfulness Intervention for Chronic Pain Management.

Background: The association between home mindfulness practice quantity in standard length mindfulness-based interventions (MBIs) and chronic pain outcomes is variable. Few studies focus on abbreviated MBIs (< 8 weeks) and distinguish between formal guided practices and informal practices in daily life. Objectives: To characterize home mindfulness practice and explore associations between home practice quantity and pre-to-post-outcome changes after an MBI for chronic pain. Methods: In this single-arm study, 21 adults with chronic pain (mean age = 54 years, 81% White, mean pain duration = 7 years) completed an MBI with four weekly group sessions. Pre and post self-report measures of pain intensity/interference, physical function, depression, anxiety, positive affect, sleep disturbance (all PROMIS measures), and pain acceptance, catastrophizing, perceived stress and mindfulness were completed, along with daily surveys of formal (mindfulness of breath, body scan) and informal (breathing space, mindfulness of daily activities) practice. Bivariate correlations and multivariable regression models were used to assess the association between days and minutes of practice and change in outcomes. Results: On average, formal practice was completed on 4.3 days per week and 13.5 minutes per day. Informal practice was completed on 3.5 days per week and 8.6 minutes per day. Formal practice was not significantly correlated with outcomes (Spearman's ρ = |.01|-|.32|), whereas informal practice was correlated with multiple outcomes (ρ = |.04|-|.66|). Number of days practiced informally was associated with improved pain interference, physical function, sleep disturbance, and catastrophizing (p's ≤ .05). Number of minutes practiced informally was associated with improved pain interference, anxiety, positive affect, and catastrophizing (p's ≤ .05). Conclusion: Informal home practice quantity, but not formal practice quantity, is associated with improved outcomes during an abbreviated MBI for chronic pain. For these MBIs, it is important to evaluate the distinct roles of formal and informal practice. ClinicalTrialsgov Registration: NCT03495856.

Disparities in Continuous Glucose Monitor Use Between Children With Type 1 Diabetes Living in Urban and Rural Areas.

OBJECTIVE: Despite evidence that continuous glucose monitoring (CGM) use is associated with lower HbA1c among children with type 1 diabetes, uptake of this technology remains lower among those with difficulty accessing health care, including those from lower socioeconomic status backgrounds and racial and ethnic minorities. In this study, we sought to explore the impact of rural location in use of CGM technology to guide patient and provider decision making. RESEARCH DESIGN AND METHODS: In this retrospective study of electronic health record demographic and visits data from a single diabetes program from 1 January 2018 through 31 December 2021, we compared the odds of completing a visit with (+) and without (-) CGM interpretation between rural-urban commuting area (RUCA) designations. RESULTS: Among the 13,645 visits completed by 2,008 patients with type 1 diabetes younger than age 18 years, we found children living in small rural towns had 31% lower odds (6.3% of CGM+ visits, 8.6% of CGM- visits; adjusted odds ratio [aOR] 0.69, 95% CI 0.51-0.94) and those living in isolated rural towns had 49% lower odds (2.0% of CGM+ visits, 3.4% of CGM- visits; aOR 0.51, 95% CI 0.28-0.92) of completing a CGM-billed clinic visit compared with those living in urban areas (70.0% of CGM+ visits, 67.2% of CGM- visits). We also found significant differences in CGM-billed visits by neighborhood deprivation as well as race/ethnicity and insurance payor. CONCLUSIONS: Geographic location presents a meaningful barrier to access to care for patients living with type 1 diabetes. Further work is needed to identify and address the needs of children and families living in rural areas to improve the care of these patients.

Third mortality follow-up of the Mallinckrodt uranium processing workers, 1942-2019.

INTRODUCTION: Mallinckrodt Chemical Works was a uranium processing facility during the Manhattan Project from 1942 to 1966. Thousands of workers were exposed to low-dose-rates of ionizing radiation from external and internal sources. This third follow-up of 2514 White male employees updates cancer and noncancer mortality potentially associated with radiation and silica dust. MATERIALS AND METHODS: Individual, annualized organ doses were estimated from film badge records (n monitored = 2514), occupational chest x-rays (n = 2514), uranium urinalysis (n = 1868), radium intake through radon breath measurements (n = 487), and radon ambient measurements (n = 1356). Silica dust exposure from pitchblende processing was estimated (n = 1317). Vital status and cause of death determination through 2019 relied upon the National Death Index and Social Security Administration Epidemiological Vital Status Service. The analysis included standardized mortality ratios (SMRs), Cox proportional hazards, and Poisson regression models. RESULTS: Vital status was confirmed for 99.4% of workers (84.0% deceased). For a dose weighting factor of 1 for intakes of uranium, radium, and radon decay products, the mean and median lung doses were 65.6 and 29.9 mGy, respectively. SMRs indicated a difference in health outcomes between salaried and hourly workers, and more brain cancer deaths than expected [SMR: 1.79; 95% confidence interval (CI): 1.14, 2.70]. No association was seen between radiation and lung cancer [hazard ratio (HR) at 100 mGy: 0.93; 95%CI: 0.78, 1.11]. The relationship between radiation and kidney cancer observed in the previous follow-up was maintained (HR at 100 mGy: 2.07; 95%CI: 1.12, 3.79). Cardiovascular disease (CVD) also increased significantly with heart dose (HR at 100 mGy: 1.11; 95%CI: 1.02, 1.21). Exposures to dust ≥23.6 mg/m3-year were associated with nonmalignant kidney disease (NMKD) (HR: 3.02; 95%CI: 1.12, 8.16) and kidney cancer combined with NMKD (HR: 2.46; 95%CI: 1.04, 5.81), though without evidence of a dose-response per 100 mg/m3-year. CONCLUSIONS: This third follow-up of Mallinckrodt uranium processors reinforced the results of the previous studies. There was an excess of brain cancers compared with the US population, although no radiation dose-response was detected. The association between radiation and kidney cancer remained, though potentially due to few cases at higher doses. The association between levels of silica dust ≥23.6 mg/m3-year and NMKD also remained. No association was observed between radiation and lung cancer. A positive dose-response was observed between radiation and CVD; however, this association may be confounded by smoking, which was unmeasured. Future work will pool these data with other uranium processing worker cohorts within the Million Person Study.

Poor Agreement Between Preoperative Transthoracic Echocardiography and Intraoperative Transesophageal Echocardiography for Grading Diastolic Dysfunction.

BACKGROUND: Guidelines for the evaluation and grading of diastolic dysfunction are available for transthoracic echocardiography (TTE). Transesophageal echocardiography (TEE) is used for this purpose intraoperatively but the level of agreement between these 2 imaging modalities for grading diastolic dysfunction is unknown. We assessed agreement between awake preoperative TTE and intraoperative TEE for grading diastolic dysfunction. METHODS: In 98 patients undergoing cardiac surgery, key Doppler measurements were obtained using TTE and TEE at the following time points: TTE before anesthesia induction (TTEawake), TTE following anesthesia induction (TTEanesth), and TEE following anesthesia induction (TEEanesth). The primary endpoint was grade of diastolic dysfunction categorized by a simplified algorithm, and measured by TTEawake and TEEanesth, for which the weighted κ statistic assessed observed agreement beyond chance. Secondary endpoints were peak early diastolic lateral mitral annular tissue velocity (e'lat) and the ratio of peak early diastolic mitral inflow velocity (E) to e'lat (E/e'lat), measured by TTEawake and TEEanesth, were compared using Bland-Altman limits of agreement. RESULTS: Disagreement in grading diastolic dysfunction by ≥1 grade occurred in 43 (54%) of 79 patients and by ≥2 grades in 8 (10%) patients with paired measurements for analysis, yielding a weighted κ of 0.35 (95% confidence interval [CI], 0.19-0.51) for the observed level of agreement beyond chance. Bland-Altman analysis of paired data for e'lat and E/e'lat demonstrated a mean difference (95% CI) of 0.51 (-0.06 to 1.09) and 0.70 (0.07-1.34), respectively, for measurements made by TTEawake compared to TEEanesth. The percentage (95% CI) of paired measurements for e'lat and E/e'lat that lay outside the [-2, +2] study-specified boundary of acceptable agreement was 36% (27%-48%) and 39% (29%-51%), respectively. Results were generally robust to sensitivity analyses, including comparing measurements between TTEawake and TTEanesth, between TTEanesth and TEEanesth, and after regrading diastolic dysfunction by the American Society of Echocardiography (ASE)/European Association of CardioVascular Imaging (EACVI) algorithm. CONCLUSIONS: There was poor agreement between TTEawake and TEEanesth for grading diastolic dysfunction by a simplified algorithm, with disagreement by ≥1 grade in 54% and by ≥2 grades in 10% of the evaluable cohort. Future studies, including comparing the prognostic utility of TTEawake and TEEanesth for clinically important adverse outcomes that may be a consequence of diastolic dysfunction, are needed to understand whether this disagreement reflects random variability in Doppler variables, misclassification by the changed technique and physiological conditions of intraoperative TEE, or the accurate detection of a clinically relevant change in diastolic dysfunction.

A Case Series of Potential Pediatric Cyanotoxin Exposures Associated with Harmful Algal Blooms in Northwest Ohio.

Cyanobacterial harmful algal blooms (CyanoHABs) are increasing in prevalence and severity in the Great Lakes region, as well as both globally and locally. CyanoHABs have the potential to cause adverse effects on human health due to the production of cyanotoxins from cyanobacteria. Common routes of exposure include recreational exposure (swimming, skiing, and boating), ingestion, and aerosolization of contaminated water sources. Cyanotoxins have been shown to adversely affect several major organ systems contributing to hepatotoxicity, gastrointestinal distress, and pulmonary inflammation. We present three pediatric case reports that coincided with CyanoHABs exposure with a focus on presentation of illness, diagnostic work-up, and treatment of CyanoHAB-related illnesses. Potential cyanotoxin exposure occurred while swimming in the Maumee River and Maumee Bay of Lake Erie in Ohio during the summer months with confirmed CyanoHAB activity. Primary symptoms included generalized macular rash, fever, vomiting, diarrhea, and severe respiratory distress. Significant labs included leukocytosis and elevated C-reactive protein. All patients ultimately recovered with supportive care. Symptoms following potential cyanotoxin exposure coincide with multiple disease states representing an urgent need to develop specific diagnostic tests of exposure.

Model-Guided Decision-Making for Thromboprophylaxis and Hospital-Acquired Thromboembolic Events Among Hospitalized Children and Adolescents: The CLOT Randomized Clinical Trial.

Importance: Rates of hospital-acquired venous thromboembolism (HA-VTE) are increasing among pediatric patients. Identifying at-risk patients for whom prophylactic interventions should be considered remains challenging. Objective: To determine whether use of a previously validated HA-VTE prognostic model, together with pediatric hematologist review, could reduce pediatric inpatient rates of HA-VTE. Design, Setting, and Participants: This pragmatic randomized clinical trial was performed from November 2, 2020, through January 31, 2022, at a single-center academic children's hospital (Monroe Carell Jr Children's Hospital at Vanderbilt). All pediatric hospital admissions (aged <22 years) under inpatient status were included and randomized. Intervention: All patients had an HA-VTE probability automatically calculated daily, which was visible to the hematology research team for patients in the intervention group. Patients with an elevated risk (predicted probability ≥2.5%) underwent additional medical record review by the research team to determine eligibility for thromboprophylaxis. Main Outcomes and Measures: The primary outcome was rate of HA-VTE. Secondary outcomes included rates of prophylactic anticoagulation and anticoagulation-associated bleeding events. Results: A total of 17 427 hospitalizations met eligibility criteria, were randomized, and were included in the primary analysis: patients had a median (IQR) age of 1.7 (0 to 11.1) years; there were 9143 (52.5%) female patients and 8284 (47.5%) male patients, and there were 445 (2.6%) Asian patients, 2739 (15.9%) Black patients, and 11 752 (67.4%) White patients. The 2 groups were evenly balanced in number (8717 in the intervention group and 8710 in the control group) and patient characteristics. A total of 58 patients (0.7%) in the control group and 77 (0.9%) in the intervention group developed HA-VTE (risk difference: 2.2 per 1000 patients; 95% CI, -0.4 to 4.8 per 1000 patients; P = .10). Recommendations to initiate thromboprophylaxis were accepted by primary clinical teams 25.8% of the time (74 of 287 hospitalizations). Minor bleeding events were rare among patients who received anticoagulation (3 of 74 [4.1%]), and no major bleeding events were observed during the study period. Among patients randomized to the control group, the model exhibited high discrimination accuracy (C statistic, 0.799, 95% CI, 0.725 to 0.856). Conclusions and Relevance: In this randomized clinical trial of the use of a HA-VTE prognostic model to reduce pediatric inpatient rates of HA-VTE, despite the use of an accurate and validated prognostic model for HA-VTE, there was substantial reluctance by primary clinical teams to initiate thromboprophylaxis as recommended. In this context, rates of HA-VTE between the control and intervention groups were not different. Future research is needed to identify improved strategies for prevention of HA-VTE and to overcome clinician concerns regarding thromboprophylaxis. Trial Registration: ClinicalTrials.gov Identifier: NCT04574895.

Screening for the high-need population using single institution versus state-wide admissions discharge transfer feed.

BACKGROUND: Access to programs for high-needs patients depending on single-institution electronic health record data (EHR) carries risks of biased sampling. We investigate a statewide admission, discharge, and transfer feed (ADT) in assessing equity in access to these programs. METHODS: This is a retrospective cross-sectional study. We included high-need patients at Vanderbilt University Medical Center (VUMC) 18 years or older, with at least three emergency visits (ED) or hospitalizations in Tennessee from January 1 to June 30, 2021, including at least one at VUMC. We used the Tennessee ADT database to identify high-need patients with at least one VUMC ED/hospitalization. Then, we compared this population with high-need patients identified using VUMC's Epic® EHR database. The primary outcome was the sensitivity of VUMC-only criteria for identifying high-need patients compared to the statewide ADT reference standard. RESULTS: We identified 2549 patients with at least one ED/hospitalization and assessed them as high-need based on the statewide ADT. Of those, 2100 had VUMC-only visits, and 449 had VUMC and non-VUMC visits. VUMC-only visit screening criteria showed high sensitivity (99.1%, 95% CI: 98.7 - 99.5%), showing that the high-needs patients admitted to VUMC infrequently access alternative systems. Results showed no meaningful difference in sensitivity when stratified by patient's race or insurance. CONCLUSIONS: ADT allows examination for potential selection bias when relying upon single-institution utilization. In VUMC's high-need patients, there's minimal selection bias when depending on same-site utilization. Further research must understand how biases vary by site and durability over time.

Radiation exposure and leukaemia risk among cohorts of persons exposed to low and moderate doses of external ionising radiation in childhood.

BACKGROUND: Many high-dose groups demonstrate increased leukaemia risks, with risk greatest following childhood exposure; risks at low/moderate doses are less clear. METHODS: We conducted a pooled analysis of the major radiation-associated leukaemias (acute myeloid leukaemia (AML) with/without the inclusion of myelodysplastic syndrome (MDS), chronic myeloid leukaemia (CML), acute lymphoblastic leukaemia (ALL)) in ten childhood-exposed groups, including Japanese atomic bomb survivors, four therapeutically irradiated and five diagnostically exposed cohorts, a mixture of incidence and mortality data. Relative/absolute risk Poisson regression models were fitted. RESULTS: Of 365 cases/deaths of leukaemias excluding chronic lymphocytic leukaemia, there were 272 AML/CML/ALL among 310,905 persons (7,641,362 person-years), with mean active bone marrow (ABM) dose of 0.11 Gy (range 0-5.95). We estimated significant (P < 0.005) linear excess relative risks/Gy (ERR/Gy) for: AML (n = 140) = 1.48 (95% CI 0.59-2.85), CML (n = 61) = 1.77 (95% CI 0.38-4.50), and ALL (n = 71) = 6.65 (95% CI 2.79-14.83). There is upward curvature in the dose response for ALL and AML over the full dose range, although at lower doses (<0.5 Gy) curvature for ALL is downwards. DISCUSSION: We found increased ERR/Gy for all major types of radiation-associated leukaemia after childhood exposure to ABM doses that were predominantly (for 99%) <1 Gy, and consistent with our prior analysis focusing on <100 mGy.

COVID-19 severity and cardiovascular outcomes in SARS-CoV-2-infected patients with cancer and cardiovascular disease.

Background: Data regarding outcomes among patients with cancer and co-morbid cardiovascular disease (CVD)/cardiovascular risk factors (CVRF) after SARS-CoV-2 infection are limited. Objectives: To compare Coronavirus disease 2019 (COVID-19) related complications among cancer patients with and without co-morbid CVD/CVRF. Methods: Retrospective cohort study of patients with cancer and laboratory-confirmed SARS-CoV-2, reported to the COVID-19 and Cancer Consortium (CCC19) registry from 03/17/2020 to 12/31/2021. CVD/CVRF was defined as established CVD or no established CVD, male ≥ 55 or female ≥ 60 years, and one additional CVRF. The primary endpoint was an ordinal COVID-19 severity outcome including need for hospitalization, supplemental oxygen, intensive care unit (ICU), mechanical ventilation, ICU or mechanical ventilation plus vasopressors, and death. Secondary endpoints included incident adverse CV events. Ordinal logistic regression models estimated associations of CVD/CVRF with COVID-19 severity. Effect modification by recent cancer therapy was evaluated. Results: Among 10,876 SARS-CoV-2 infected patients with cancer (median age 65 [IQR 54-74] years, 53% female, 52% White), 6253 patients (57%) had co-morbid CVD/CVRF. Co-morbid CVD/CVRF was associated with higher COVID-19 severity (adjusted OR: 1.25 [95% CI 1.11-1.40]). Adverse CV events were significantly higher in patients with CVD/CVRF (all p<0.001). CVD/CVRF was associated with worse COVID-19 severity in patients who had not received recent cancer therapy, but not in those undergoing active cancer therapy (OR 1.51 [95% CI 1.31-1.74] vs. OR 1.04 [95% CI 0.90-1.20], pinteraction <0.001). Conclusions: Co-morbid CVD/CVRF is associated with higher COVID-19 severity among patients with cancer, particularly those not receiving active cancer therapy. While infrequent, COVID-19 related CV complications were higher in patients with comorbid CVD/CVRF. (COVID-19 and Cancer Consortium Registry [CCC19]; NCT04354701).