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Wastewater-based epidemiology (WBE) has been deployed broadly as an early warning tool for emerging COVID-19 outbreaks. WBE can inform targeted interventions and identify communities with high transmission, enabling quick and effective responses. As the wastewater (WW) becomes an increasingly important indicator for COVID-19 transmission, more robust methods and metrics are needed to guide public health decision-making. This research aimed to develop and implement a mathematical framework to infer incident cases of COVID-19 from SARS-CoV-2 levels measured in WW. We propose a classification scheme to assess the adequacy of model training periods based on clinical testing rates and assess the sensitivity of model predictions to training periods. A testing period is classified as adequate when the rate of change in testing is greater than the rate of change in cases. We present a Bayesian deconvolution and linear regression model to estimate COVID-19 cases from WW data. The effective reproductive number is estimated from reconstructed cases using WW. The proposed modeling framework was applied to three Northern California communities served by distinct WW treatment plants. The results showed that training periods with adequate testing are essential to provide accurate projections of COVID-19 incidence.

BackgroundApproximately 5% of cancer patients in the United States presented with metastatic bone disease (MBD) at diagnosis. Current study explores the disparities in survival for patients with MBD.MethodsPatients with the diagnosis of MBD at presentation for the five most common primary anatomical sites were extracted from Surveillance, Epidemiology, and End Results Census tract-level dataset (2010-2016). Kaplan-Meier and Cox Proportional Hazard models were used to evaluate survival, and prognostic factors for each cohort. Prognostic significance of socioeconomic status (SES) and insurance status were ascertained.ResultsThe five most common anatomical-sites with MBD at presentation included "lung" (n = 59 739), "prostate" (n = 19 732), "breast" (n = 16 244), "renal and urothelium" (n = 7718) and "colon" (n= 3068). Lower SES was an independent risk factor for worse disease-specific survival (DSS) for patients with MBD originating from lung, prostate, breast and colon. Lack of insurance was an independent risk factor for worse DSS for MBD patients with primary tumors in lung and breast.ConclusionsMBD patients from the five most common primary sites demonstrated SES and insurance-related disparities in disease-specific survival. This is the first and largest study to explore SES and insurance-related disparities among patients specifically afflicted with MBD. Our findings highlight vulnerability of patients with MBD across multiple primary sites to financial toxicity.

BackgroundAdolescent and young adult (AYA) patients with cancer are underrepresented on cancer clinical trials (CCTs), and most AYAs are treated in the community setting. Past research has focused on individual academic institutions, but factors impacting enrollment vary across institutions. Therefore, we examined the patterns of barriers and facilitators between high- and low-AYA enrolling community-based clinics to identify targets for intervention.Materials and methodsWe conducted 34 semi-structured interviews with stakeholders employed used at National Cancer Institute Community Oncology Research Program (NCORP) affiliate sites ("clinics"). Stakeholders (eg, clinical research associates, patient advocates) were recruited from high- and low-AYA enrolling clinics. We conducted a content analysis and calculated the percentage of stakeholders from each clinic type that reported the barrier or facilitator. A 10% gap between high- and low-enrollers was considered the threshold for differences.ResultsBoth high- and low-enrollers highlighted insufficient resources as a barrier and the presence of a patient eligibility screening process as a facilitator to AYA enrollment. High-enrolling clinics reported physician gatekeeping as a barrier and the improvement of departmental collaboration as a facilitator. Low-enrollers reported AYAs' uncertainty regarding the CCT process as a barrier and the need for increased physician endorsement of CCTs as a facilitator.ConclusionsHigh-enrolling clinics reported more barriers downstream in the enrollment process, such as physician gatekeeping. In contrast, low-enrolling clinics struggled with the earlier steps in the CCT enrollment process, such as identifying eligible trials. These findings highlight the need for multi-level, tailored interventions rather than a "one-size-fits-all" approach to improve AYA enrollment in the community setting.

Implementation science (IS) has garnered attention within oncology, and most prior IS work has focused on adult, not pediatric, oncology. This narrative review broadly characterizes IS for pediatric oncology. It includes studies through 2020 using the following search terms in PubMed, Ovid Medline, and Cochrane: "implementation science," "pediatric," "childhood," "cancer," and "oncology." Systematic review was not performed due to the limited number of heterogeneous studies. Of 216 articles initially reviewed, nine were selected as specific to IS and pediatric oncology. All nine examined oncologic supportive care, cancer prevention, or cancer control. The supportive care focus is potentially due to the presence of cooperative study groups such as the Children's Oncology Group, which efficiently drive cancer-directed therapy changes through clinical trials. Future IS within pediatric oncology should embrace this ecosystem and focus on cancer control interventions that benefit patients across multiple cancer types and patients treated outside cooperative group studies.

BackgroundWe have analyzed sex, race/ethnicity or socioeconomic disparities in the incidence of metastatic bone disease (MBD).MethodsPatients with the diagnosis of MBD at presentation for five most common primary anatomical sites was extracted from Surveillance, Epidemiology, and End Results Census tract-level dataset. Mean incidence of MBD for different sex, racial/ethnic and socioeconomic groups were compared.ResultsThe five most common anatomical sites with MBD at presentation include "lung: (n = 59 739), "prostate" (n = 19 732), "breast" (n = 16 244), "renal" (n = 7718) and "colon" (n = 3068). There was an increase in incidence of MBD among cancers originating from prostate (annual percentage change [APC] 4.94), renal (APC 2.55), and colon (APC 3.21) (p

Few studies have explored interventions to improve adolescent and young adult (AYA) cancer care delivery. While many AYAs receive cancer care at NCI Community Oncology Research Program (NCORP) sites, few enroll on clinical trials. Barriers and facilitators to pediatric oncologist activation of and enrollment on an AYA cross-network National Clinical Trials Network (NCTN) supportive care trial were assessed using a survey that was administered to 162 stakeholders representing all 47 children's oncology group (COG) institutions affiliated to an NCORP. Fifty-eight stakeholders participated representing 62% of all sites surveyed. Approximately half of participants (45%) were unaware of the trial. Seven sites had the study open and one enrolled a patient. Reasons for not opening and enrolling on the trial included limited research staff and resources, low anticipated accrual, and lower prioritization of the trial. Enrollment facilitators included having a local "AYA champion," improving communication between pediatric and medical oncology, and having site education on available AYA trials. Interventions focused on increasing site and provider awareness of AYA trials and decreasing local barriers to AYA enrollment are needed.

SARS-CoV-2 has infected nearly 3.7 million and killed 61,722 Californians, as of May 22, 2021. Non-pharmaceutical interventions have been instrumental in mitigating the spread of the coronavirus. However, as we ease restrictions, widespread implementation of COVID-19 vaccines is essential to prevent its resurgence. In this work, we addressed the adequacy and deficiency of vaccine uptake within California and the possibility and severity of resurgence of COVID-19 as restrictions are lifted given the current vaccination rates. We implemented a real-time Bayesian data assimilation approach to provide projections of incident cases and deaths in California following the reopening of its economy on June 15, 2021. We implemented scenarios that vary vaccine uptake prior to reopening, and transmission rates and effective population sizes following the reopening. For comparison purposes, we adopted a baseline scenario using the current vaccination rates, which projects a total 11,429 cases and 429 deaths in a 15-day period after reopening. We used posterior estimates based on CA historical data to provide realistic model parameters after reopening. When the transmission rate is increased after reopening, we projected an increase in cases by 21.8% and deaths by 4.4% above the baseline after reopening. When the effective population is increased after reopening, we observed an increase in cases by 51.8% and deaths by 12.3% above baseline. A 30% reduction in vaccine uptake alone has the potential to increase cases and deaths by 35% and 21.6%, respectively. Conversely, increasing vaccine uptake by 30% could decrease cases and deaths by 26.1% and 17.9%, respectively. As California unfolds its plan to reopen its economy on June 15, 2021, it is critical that social distancing and public behavior changes continue to be promoted, particularly in communities with low vaccine uptake. The Centers for Disease Control and Prevention (CDC) recommendation to ease mask-wearing for fully vaccinated individuals despite major inequities in vaccine uptake in counties across the state highlights some of the logistical challenges that society faces as we enthusiastically phase out of this pandemic.

BackgroundAlthough it is well documented that adolescents and young adults (AYAs) with cancer have low participation in cancer clinical trials (CCTs), the underlying reasons are not well understood. We used the National Cancer Institute Community Oncology Research Program (NCORP) network to identify barriers and facilitators to AYA CCT enrollment, and strategies to improve enrollment at community-based and minority and/or underserved sites.MethodsWe performed one-on-one semistructured qualitative interviews with stakeholders (NCORP site principle investigators, NCORP administrators, physicians involved in enrollment, lead clinical research associates or clinical research nurses, nurse navigators, regulatory research associates, patient advocates) in the AYA CCT enrollment process. NCORP sites that included high and low AYA-enrolling affiliate sites and were diverse in geography and department representation (eg, pediatrics, medical oncology) were invited to participate. All interviews were recorded and transcribed. Themes related to barriers and facilitators and strategies to improve enrollment were identified.ResultsWe conducted 43 interviews across 10 NCORP sites. Eleven barriers and 13 facilitators to AYA enrollment were identified. Main barriers included perceived limited trial availability and eligibility, physician gatekeeping, lack of provider and research staff time, and financial constraints. Main facilitators and strategies to improve AYA enrollment included having a patient screening process, physician endorsement of trials, an "AYA champion" on site, and strong communication between medical and pediatric oncology.ConclusionsStakeholders identified several opportunities to address barriers contributing to low AYA CCT enrollment at community-based and minority and/or underserved sites. Results of this study will inform development and implementation of targeted interventions to increase AYA CCT enrollment.

The National Center for Advancing Translational Sciences (NCATS) has defined translation as the process of turning observations into interventions that are adopted, sustained, and improve health. Translation must attend to research and community systems and context at multiple levels, and to key stakeholders. Dissemination and implementation (D&I) sciences are informed by an understanding of the critical role of people and systems in disseminating, adopting, and sustaining innovations within real-world settings. Thus, the D&I sciences provides a set of principles that can guide the translational work of Clinical and Translational Science Award (CTSA) programs from basic research to public health. In this special communication, our cross-domain working group of the CTSA consortium, comprised of experts in methods and processes, workforce development, evaluation, stakeholder engagement, and D&I sciences, share a vision of how CTSAs can enhance translation across the translational spectrum through the integration of D&I sciences into the critical areas of methods and processes, workforce development, and evaluation. We propose a set of recommendations for NCATS national and local leaders that are intended to move D&I sciences out of a position of unfamiliarity and ancillary value and into the core identity of who CTSAs are, how they think, and what they do, to advance translation and health.

The rapid spread of the new SARS-CoV-2 virus triggered a global health crisis, disproportionately impacting people with pre-existing health conditions and particular demographic and socioeconomic characteristics. One of the main concerns of governments has been to avoid health systems becoming overwhelmed. For this reason, they have implemented a series of non-pharmaceutical measures to control the spread of the virus, with mass tests being one of the most effective controls. To date, public health officials continue to promote some of these measures, mainly due to delays in mass vaccination and the emergence of new virus strains. In this research, we studied the association between COVID-19 positivity rate and hospitalization rates at the county level in California using a mixed linear model. The analysis was performed in the three waves of confirmed COVID-19 cases registered in the state to September 2021. Our findings suggest that test positivity rate is consistently associated with hospitalization rates at the county level for all study waves. Demographic factors that seem to be related to higher hospitalization rates changed over time, as the profile of the pandemic impacted different fractions of the population in counties across California.

IntroductionStatistical literacy is essential in clinical and translational science (CTS). Statistical competencies have been published to guide coursework design and selection for graduate students in CTS. Here, we describe common elements of graduate curricula for CTS and identify gaps in the statistical competencies.MethodsWe surveyed statistics educators using e-mail solicitation sent through four professional organizations. Respondents rated the degree to which 24 educational statistical competencies were included in required and elective coursework in doctoral-level and master's-level programs for CTS learners. We report competency results from institutions with Clinical and Translational Science Awards (CTSAs), reflecting institutions that have invested in CTS training.ResultsThere were 24 CTSA-funded respondents representing 13 doctoral-level programs and 23 master's-level programs. For doctoral-level programs, competencies covered extensively in required coursework for all doctoral-level programs were basic principles of probability and hypothesis testing, understanding the implications of selecting appropriate statistical methods, and computing appropriate descriptive statistics. The only competency extensively covered in required coursework for all master's-level programs was understanding the implications of selecting appropriate statistical methods. The least covered competencies included understanding the purpose of meta-analysis and the uses of early stopping rules in clinical trials. Competencies considered to be less fundamental and more specialized tended to be covered less frequently in graduate courses.ConclusionWhile graduate courses in CTS tend to cover many statistical fundamentals, learning gaps exist, particularly for more specialized competencies. Educational material to fill these gaps is necessary for learners pursuing these activities.

Life course research embraces the complexity of health and disease development, tackling the extensive interactions between genetics and environment. This interdisciplinary blueprint, or theoretical framework, offers a structure for research ideas and specifies relationships between related factors. Traditionally, methodological approaches attempt to reduce the complexity of these dynamic interactions and decompose health into component parts, ignoring the complex reciprocal interaction of factors that shape health over time. New methods that match the epistemological foundation of the life course framework are needed to fully explore adaptive, multilevel, and reciprocal interactions between individuals and their environment. The focus of this article is to (1) delineate the differences between lifespan and life course research, (2) articulate the importance of complex systems science as a methodological framework in the life course research toolbox to guide our research questions, (3) raise key questions that can be asked within the clinical and translational science domain utilizing this framework, and (4) provide recommendations for life course research implementation, charting the way forward. Recent advances in computational analytics, computer science, and data collection could be used to approximate, measure, and analyze the intertwining and dynamic nature of genetic and environmental factors involved in health development.

BackgroundEpidemics of COVID-19 in student populations at universities were a key concern for the 2020-2021 school year. The University of California (UC) System developed a set of recommendations to reduce campus infection rates. SARS-CoV-2 test results are summarized for the ten UC campuses during the Fall 2020 term.MethodsUC mitigation efforts included protocols for the arrival of students living on-campus students, non-pharmaceutical interventions, daily symptom monitoring, symptomatic testing, asymptomatic surveillance testing, isolation and quarantine protocols, student ambassador programs for health education, campus health and safety pledges, and lowered density of on-campus student housing. We used data from UC campuses, the UC Health-California Department of Public Health Data Modeling Consortium, and the U.S. Census to estimate the proportion of each campus' student populations that tested positive for SARS-CoV-2 and compared it to the fraction individuals aged 20-29 years who tested positive in their respective counties.ResultsSARS-CoV-2 cases in campus populations were generally low in September and October 2020, but increased in November and especially December, and were highest in early to mid-January 2021, mirroring case trajectories in their respective counties. Many students were infected during the Thanksgiving and winter holiday recesses and were detected as cases upon returning to campus. The proportion of students who tested positive for SARS-CoV-2 during Fall 2020 ranged from 1.2% to 5.2% for students living on campus and was similar to students living off campus. For most UC campuses the proportion of students testing positive was lower than that for the 20-29-year-old population in which campuses were located.ConclusionsThe layered mitigation approach used on UC campuses, informed by public health science and augmented perhaps by a more compliant population, likely minimized campus transmission and outbreaks and limited transmission to surrounding communities. University policies that include these mitigation efforts in Fall 2020 along with SARS-CoV-2 vaccination, may alleviate some local concerns about college students returning to communities and facilitate resumption of normal campus operations and in-person instruction.

PurposeClinical trial participation leads to progress in cancer care. Principal investigators (PIs) and clinical research associates (CRAs) play key roles in the provision and maintenance of clinical trial portfolios at their sites. Previous studies have evaluated the educational and resource needs of adult oncology providers, but nothing to date has focused on providers of pediatric oncology care. We aimed to identify the educational needs and clinical trial participation barriers at National Cancer Institute Community Oncology Research Program (NCORP) Children's Oncology Group (COG) sites to improve the quality of site investigator engagement.MethodsQuality improvement surveys of pediatric clinical research staff at NCORP sites were performed. The first was a web-based inquiry of NCORP COG PIs and lead CRAs to assess their general understanding of NCORP organizational structure and needs. The second survey of COG PIs was conducted by one-on-one telephone interviews aimed at identifying specific barriers to physician engagement and patient enrollment in clinical trial research.ResultsThe majority of NCORP COG PIs and CRAs (63%) reported an incomplete understanding of NCORP structure, with approximately half expressing interest in developing stronger collaborations and engagement. Most NCORP COG PIs reported at least one shared barrier to clinical trial enrollment (78%), with inadequate protected time and research support (39% each) being the most frequently cited barriers.ConclusionsContributions to pediatric cancer clinical research at COG NCORP sites could be enhanced through improved education, resources, and time allocation.

PurposeWe previously demonstrated lower early mortality for young adults (YAs) with acute lymphoblastic leukemia (ALL) who received induction treatment at specialized cancer centers (SCCs) versus community hospitals. The aim of this study is to determine the impact of inpatient location of treatment throughout therapy on long-term survival, complications, and cost-associations that have not yet been evaluated at the population level.MethodsUsing the California Cancer Registry linked to a hospitalization database, we identified patients, 0-39 years of age, diagnosed with first primary ALL who received inpatient treatment between 1991 and 2014. Patients were classified as receiving all or part or none of their inpatient treatment at an SCC within 3 years of diagnosis. Inverse probability-weighted, multivariable Cox regression models estimated the associations between location of treatment and sociodemographic and clinical factors with survival. We compared 3-year inpatient costs overall and per day by age group and location of care.ResultsEighty-four percent (0-18 years; n = 4,549) of children and 36% of YAs (19-39 years; n = 683) received all treatment at SCCs. Receiving all treatment at an SCC was associated with superior leukemia-specific (hazard ratio [HR], 0.76; 95% CI, 0.67 to 0.88) and overall survival (HR, 0.87; 95% CI, 0.77 to 0.97) in children and in YAs (HR, 0.71; 95% CI, 0.61 to 0.83; HR, 0.70; 95% CI, 0.62 to 0.80) even after controlling for complications. The cost of inpatient care during the full course of therapy was higher in patients receiving all of their care at SCCs.ConclusionOur results demonstrate that inpatient treatment at an SCC throughout therapy is associated with superior survival; therefore, strong consideration should be given to referring these patients to SCCs.

IntroductionStatistical literacy is essential in clinical and translational science (CTS). Statistical competencies have been published to guide coursework design and selection for graduate students in CTS. Here, we describe common elements of graduate curricula for CTS and identify gaps in the statistical competencies.MethodsWe surveyed statistics educators using e-mail solicitation sent through four professional organizations. Respondents rated the degree to which 24 educational statistical competencies were included in required and elective coursework in doctoral-level and master's-level programs for CTS learners. We report competency results from institutions with Clinical and Translational Science Awards (CTSAs), reflecting institutions that have invested in CTS training.ResultsThere were 24 CTSA-funded respondents representing 13 doctoral-level programs and 23 master's-level programs. For doctoral-level programs, competencies covered extensively in required coursework for all doctoral-level programs were basic principles of probability and hypothesis testing, understanding the implications of selecting appropriate statistical methods, and computing appropriate descriptive statistics. The only competency extensively covered in required coursework for all master's-level programs was understanding the implications of selecting appropriate statistical methods. The least covered competencies included understanding the purpose of meta-analysis and the uses of early stopping rules in clinical trials. Competencies considered to be less fundamental and more specialized tended to be covered less frequently in graduate courses.ConclusionWhile graduate courses in CTS tend to cover many statistical fundamentals, learning gaps exist, particularly for more specialized competencies. Educational material to fill these gaps is necessary for learners pursuing these activities.

Life course research embraces the complexity of health and disease development, tackling the extensive interactions between genetics and environment. This interdisciplinary blueprint, or theoretical framework, offers a structure for research ideas and specifies relationships between related factors. Traditionally, methodological approaches attempt to reduce the complexity of these dynamic interactions and decompose health into component parts, ignoring the complex reciprocal interaction of factors that shape health over time. New methods that match the epistemological foundation of the life course framework are needed to fully explore adaptive, multilevel, and reciprocal interactions between individuals and their environment. The focus of this article is to (1) delineate the differences between lifespan and life course research, (2) articulate the importance of complex systems science as a methodological framework in the life course research toolbox to guide our research questions, (3) raise key questions that can be asked within the clinical and translational science domain utilizing this framework, and (4) provide recommendations for life course research implementation, charting the way forward. Recent advances in computational analytics, computer science, and data collection could be used to approximate, measure, and analyze the intertwining and dynamic nature of genetic and environmental factors involved in health development.

BackgroundFew adolescents and young adults (AYAs, 15-39 years old) enroll onto cancer clinical trials, which hinders research otherwise having the potential to improve outcomes in this unique population. Prior studies have reported that AYAs are more likely to receive cancer care in community settings. The National Cancer Institute (NCI) has led efforts to increase trial enrollment through its network of NCI-designated cancer centers (NCICC) combined with community outreach through its Community Clinical Oncology Program (CCOP; replaced by the NCI Community Oncology Research Program in 2014).MethodsUsing AYA proportional enrollment (the proportion of total enrollments who were AYAs) as the primary outcome, we examined enrollment of AYAs onto SWOG therapeutic trials at NCICC, CCOP, and non-NCICC/non-CCOP sites from 2004 to 2013 by type of site, study period (2004-08 vs 2009-13), and patient demographics.ResultsOverall, AYA proportional enrollment was 10.1%. AYA proportional enrollment decreased between 2004-2008 and 2009-2013 (13.1% vs 8.5%, P

BackgroundCardiopulmonary assessment for lung resection is important for risk stratification, and the American College of Chest Physicians (ACCP) guidelines provide decision support. We ascertained the cardiopulmonary assessment practices of thoracic surgeons and determined whether they are guideline concordant.MethodsAn anonymous survey was emailed to 846 thoracic surgeons who participate in The Society of Thoracic Surgeons General Thoracic Surgery Database. We analyzed survey responses by practice type (general thoracic [GT] versus cardiothoracic [CT]) and years in practice (0-9, 10-19, and ≥20) with the use of contingency tables. We compared adherence of survey responses with the guidelines.ResultsThe response rate was 24.0% (n = 203). Most surgeons (n = 121, 59.6%) cited a predicted postoperative forced expiratory volume in 1 second or diffusing capacity of lung for carbon monoxide threshold of 40% for further evaluation. Experienced surgeons (≥20 years) were more likely to have a threshold that varies by surgical approach (31.3% versus 23.5% with 10-19 years of experience and 15.9% for 0-9 years of experience, P = .007). Overall, 52.2% refer patients with cardiovascular risk factors to cardiology and 42.9% refer patients with abnormal stress testing. CT surgeons were more likely to refer all patients to cardiology than GT surgeons (17.6% versus 2.4%, P < .001). Only one respondent (0.5%) was 100% adherent to the ACCP guidelines, and 4.4% and 45.8% were 75% and 50% adherent, respectively.ConclusionsAmong thoracic surgeons, there is variation in preoperative cardiopulmonary assessment practices, with differences by practice type and years in practice, and marked discordance with the ACCP guidelines. Further study of guideline adherence linked to postoperative morbidity and mortality is warranted to determine whether adherence affects outcomes.

Recognition and treatment of malnutrition in pediatric oncology patients is crucial because it is associated with increased morbidity and mortality. Nutrition-relevant data collected from cancer clinical trials and nutrition-specific studies are insufficient to drive high-impact nutrition research without augmentation from additional data sources. To date, clinical big data resources are underused for nutrition research in pediatric oncology. Health-care big data can be broadly subclassified into three clinical data categories: administrative, electronic health record (including clinical data research networks and learning health systems), and mobile health. Along with -omics data, each has unique applications and limitations. We summarize the potential use of clinical big data to drive pediatric oncology nutrition research and identify key scientific gaps. A framework for advancement of big data utilization for pediatric oncology nutrition research is presented and focuses on transdisciplinary teams, data interoperability, validated cohort curation, data repurposing, and mobile health applications.

BackgroundTo determine whether telemedicine improves access to outpatient neurology care for underserved patients, we compared appointment completion between urban, in-person clinics and telemedicine clinics held in rural and underserved communities where neurology consultations are provided remotely.MethodsIn this retrospective study, we identified patients scheduled for outpatient care from UCDH pediatric neurologists between January 1, 2009, and July 31, 2017, in person and by telemedicine. Demographic and clinical variables were abstracted from electronic medical records. We evaluated the association between consultation modality and visit completion in overall and matched samples using hierarchical multivariable logistic regression.ResultsWe analyzed 13,311 in-person appointments by 3,831 patients and 1,158 telemedicine appointments by 381 patients. The average travel time to the site of care was 45.8 ± 52.1 minutes for the in-person cohort and 22.3 ± 22.7 minutes for the telemedicine cohort. Telemedicine sites were located at an average travel time of 217.1 ± 114.8 minutes from UCDH. Telemedicine patients were more likely to have nonprivate insurance, lower education, and lower household income. They had different diagnoses and fewer complex chronic conditions. Telemedicine visits were more likely to be completed than either "cancelled" or missed ("no show") compared with in-person visits (OR 1.57, 95% CI: 1.34-1.83; OR 1.66, 95% CI: 1.31-2.10 matched on travel time to the site of care; OR 2.22, 95% CI: 1.66-2.98 matched on travel time to UCDH).ConclusionsThe use of telemedicine for outpatient pediatric neurology visits has high odds of completion and can serve as an equal adjunct to in-person clinic visits.

e21515 Background: While cancer is the leading cause of non-accidental death in children and AYAs, factors associated with delays in diagnosis in young patients with cancer are poorly understood; we sought to fill this knowledge gap. Methods: Using the OptumLabs Data Warehouse’s claims data for commercially insured enrollees in a large US health plan—we identified pediatric [0-14 years (y)] and AYA (15–39 y) patients diagnosed with soft tissue sarcomas (STS), bone tumors (BT) and germ cell tumors (GCT) during 2001–17 and continuously enrolled 6 months prior to diagnosis. Time to diagnosis was calculated as days between first medical encounter associated with a possible cancer symptom and diagnosis date. Median times from first symptom to diagnosis were compared using Wilcoxon Rank Sum test. Multivariable logistic regression identified sociodemographic and clinical factors associated with longer time ( > 3 months) from symptom to diagnosis. Results: Of the 11,395 patients, 86% presented to medical care with symptoms prior to diagnosis [STS: 2,228 (89%); BT: 1,565 (87%); GCT: 5,904 (84%)]. The most common symptoms were pain and swelling. STS had the longest median days to diagnosis (92), followed by BT (91) and GCT (49). There was a significant difference (p < 0.001) in median days to diagnosis by age for BT (0–14y: 69; 15–21y: 77; 22–39y: 105) and GCT (0–14y: 96; 15–21y: 34; 22–39y: 49), but not for STS. Patients in households with ≥ a college degree (OR 1.96, 95% CI 1.06–3.64, vs < high school) and seeing a specialist (excluding oncologists) (OR 2.54, CI 2.03–3.19, vs primary care) at first symptom presentation was associated with a longer delay, while older age (22–39y: OR 0.77, CI 0.63–0.94, vs 0-14y) and male sex (OR 0.58, CI 0.51–0.66) were associated with a shorter delay in diagnosis. Conclusions: This study demonstrates that, in a commercially insured population, time to diagnosis varies by cancer type and is impacted by clinical and sociodemographic factors. Shorter time to diagnosis may represent delays in presenting to medical care or more acute presentations of symptoms, therefore patient-reported symptoms and barriers to care data should be collected to better define strategies to reduce delays in diagnosis.

e18138 Background: Patients diagnosed with leukemia and lymphoma typically present with nonspecific symptoms, making a timely diagnosis difficult. Little is known about factors associated with delays in diagnosis. We hypothesized that age, minority race/ethnicity, and low income are associated with greater time to diagnosis. Methods: Using the OptumLabs Data Warehouse, which includes claims data for privately insured enrollees in a large US health plan, we identified 17,536 pediatric (0-14 y), adolescent (15-21 y), and young adult (22-39 y) patients diagnosed with acute leukemia or lymphoma between 2001-17. Using this retrospective cohort, potential cancer-related symptoms occurring up to 6 months pre-diagnosis were identified. Delay was defined as > 3 months from symptom onset to diagnosis. Contingency table analysis with chi-squared tests and unconditional logistic regression were used to estimate the association between sociodemographic factors and delays in diagnosis. Results: Seventy-eight percent of patients had a diagnosis of a cancer-related symptom in the 6 months prior to diagnosis. The most common presenting symptoms were lymphadenopathy, fever, and cytopenias. The median days to diagnosis was longer in young adults (93) than children (86) or adolescents (81) (p = < 0.0001). For pediatric v. AYA patients, median days to diagnosis differed for those with constitutional symptoms (18 v. 37, p = < 0.001), infectious symptoms (93 v. 74, p = < 0.001), and cytopenias (11 v. 22, p = < 0.001). Multivariable analysis identified younger age, female sex, and low household income to be significantly associated with delays in diagnosis (table below). Conclusions: In this large cohort of privately insured patients, adolescents had the shortest time to diagnosis. We saw no disparities by race/ethnicity or education but observed that low income ( < $40K) and female patients had greater odds of delays in diagnosis. [Table: see text]

BackgroundSmoking is a risk factor for complications after lung resection. Our primary aim was to ascertain thoracic surgeons' beliefs and practices on smoking cessation before lung resection.MethodsAn anonymous survey was emailed to 846 thoracic surgeons who participate in The Society of Thoracic Surgeons General Thoracic Surgery Database.ResultsThe response rate was 23.6% (n = 200). Surgeons were divided when asked whether it is ethical to require that patients quit smoking (yes, n = 96 [48%]) and whether it is fair to have their outcomes affected by patients who do not quit (yes, n = 87 [43.5%]). Most do not require smoking cessation (n = 120 [60%]). Of those who require it, the most common required period of cessation is 2 weeks or more. Most believe that patient factors are the main barrier to quitting (n = 160 [80%]). Risk of disease progression (39% vs 17.5%, p = 0.02) and alienating patients (17.5% vs 8.8%, p = 0.04) were very important considerations of those who do not require smoking cessation versus those who do. Only 19 (9.5%) always refer to a smoking cessation program and prescribe nicotine replacement therapy and even fewer, 9 (4.5%), always refer to a program and prescribe medical therapy.ConclusionsThoracic surgeons are divided on their beliefs and practices regarding smoking cessation before lung resection. Most believe patient factors are the main barrier to quitting and have concerns about disease progression while awaiting cessation. Very few surgeons refer to a smoking cessation program and prescribe nicotine replacement therapy or medical therapy.

ObjectivesStudies suggest that a restrictive transfusion strategy is safe in burns, yet the efficacy of a restrictive transfusion policy in massive burn injury is uncertain. Our objective: compare outcomes between massive burn (≥60% total body surface area (TBSA) burn) and major (20-59% TBSA) burn using a restrictive or a liberal blood transfusion strategy.MethodsPatients with burns ≥20% were block randomized by age and TBSA to a restrictive (transfuse hemoglobin 0.05).ConclusionsA restrictive transfusion strategy may be beneficial in massive burns in reducing ventilator days, ICU days and blood utilization, but does not decrease infection, mortality, hospital LOS or wound healing.

BackgroundStagnant outcomes for adolescents and young adults (AYAs) 15-39 years of age with cancer are partly attributed to poor enrollment onto clinical trials. Initiatives have focused on increasing accrual, but changes at the population-level are unknown. We examined patterns of clinical trial participation over time in AYA patients with cancer.ProcedureWe utilized medical record data from AYAs in two population-based National Cancer Institute Patterns of Care Studies identified through the Surveillance, Epidemiology and End Results Program. Among 3135 AYAs diagnosed with non-Hodgkin lymphoma (NHL), Hodgkin lymphoma, acute lymphoblastic leukemia (ALL), and sarcoma, we used multivariate logistic regression to evaluate patient and provider characteristics associated with clinical trial enrollment. Interaction terms evaluated variation in clinical trial enrollment across patient and provider characteristics by year of diagnosis.ResultsFrom 2006 to 2012-2013, clinical trial participation increased from 14.8% to 17.9% (P

ObjectivesMajor trials examining storage age of blood transfused to critically ill patients administered relatively few blood transfusions. We sought to determine if the storage age of blood affects outcomes when very large amounts of blood are transfused.DesignA secondary analysis of the multicenter randomized Transfusion Requirement in Burn Care Evaluation study which compared restrictive and liberal transfusion strategies.SettingEighteen tertiary-care burn centers.PatientsTransfusion Requirement in Burn Care Evaluation evaluated 345 adults with burns greater than or equal to 20% of the body surface area. We included only the 303 patients that received blood transfusions.InterventionsThe storage ages of all transfused red cell units were collected during Transfusion Requirement in Burn Care Evaluation. A priori measures of storage age were the the mean storage age of all transfused blood and the proportion of all transfused blood considered very old (stored ≥ 35 d).Measurements and main resultsThe primary outcome was the severity of multiple organ dysfunction. Secondary outcomes included time to wound healing, the duration of mechanical ventilation, and in-hospital mortality. There were 6,786 red cell transfusions with a mean (± SD) storage age of 25.6 ± 10.2 days. Participants received a mean of 23.4 ± 31.2 blood transfusions (range, 1-219) and a mean of 5.3 ± 10.7 units of very old blood. Neither mean storage age nor proportion of very old blood had any influence on multiple organ dysfunction severity, time to wound healing, or mortality. Duration of ventilation was significantly predicted by both mean blood storage age and the proportion of very old blood, but this was of questionable clinical relevance given extreme variability in duration of ventilation (adjusted r ≤ 0.01).ConclusionsDespite massive blood transfusion, including very old blood, the duration of red cell storage did not influence outcome in burn patients. Provision of the oldest blood first by Blood Banks is rational, even for massive transfusion.

Cisplatin is an essential chemotherapeutic agent in the treatment of many pediatric cancers. Unfortunately, cisplatin-induced hearing loss (CIHL) is a common, clinically significant side effect with life-long ramifications, particularly for young children. ACCL05C1 and ACCL0431 are two recently completed Children's Oncology Group studies focused on the measurement and prevention of CIHL. The purpose of this paper was to gain insights from ACCL05C1 and ACCL0431, the first published cooperative group studies dedicated solely to CIHL, to inform the design of future pediatric otoprotection trials. Use of otoprotective agents is an attractive strategy for preventing CIHL, but their successful development must overcome a unique constellation of methodological challenges related to translating preclinical research into clinical trials that are feasible, evaluate practical interventions, and limit risk. Issues particularly important for children include use of appropriate methods for hearing assessment and CIHL severity grading, and use of trial designs that are well-informed by preclinical models and suitable for relatively small sample sizes. Increasing interest has made available new funding opportunities for expanding this urgently needed research.

ObjectiveOur objective was to compare outcomes of a restrictive to a liberal red cell transfusion strategy in 20% or more total body surface area (TBSA) burn patients. We hypothesized that the restrictive group would have less blood stream infection (BSI), organ dysfunction, and mortality.BackgroundPatients with major burns have major (>1 blood volume) transfusion requirements. Studies suggest that a restrictive blood transfusion strategy is equivalent to a liberal strategy. However, major burn injury is precluded from these studies. The optimal transfusion strategy in major burn injury is thus needed but remains unknown.MethodsThis prospective randomized multicenter trial block randomized patients to a restrictive (hemoglobin 7-8 g/dL) or liberal (hemoglobin 10-11 g/dL) transfusion strategy throughout hospitalization. Data collected included demographics, infections, transfusions, and outcomes.ResultsEighteen burn centers enrolled 345 patients with 20% or more TBSA burn similar in age, TBSA burn, and inhalation injury. A total of 7054 units blood were transfused. The restrictive group received fewer blood transfusions: mean 20.3 ± 32.7 units, median = 8 (interquartile range: 3, 24) versus mean 31.8 ± 44.3 units, median = 16 (interquartile range: 7, 40) in the liberal group (P < 0.0001, Wilcoxon rank sum). BSI incidence, organ dysfunction, ventilator days, and time to wound healing (P > 0.05) were similar. In addition, there was no 30-day mortality difference: 9.5% restrictive versus 8.5% liberal (P = 0.892, χ test).ConclusionsA restrictive transfusion strategy halved blood product utilization. Although the restrictive strategy did not decrease BSI, mortality, or organ dysfunction in major burn injury, these outcomes were no worse than the liberal strategy (Clinicaltrials.gov identifier NCT01079247).

PurposeTo investigate associations of sociodemographic factors-race/ethnicity, neighborhood socioeconomic status (SES), and health insurance-with survival for adolescents and young adults (AYAs) with invasive cancer.MethodsData on 80,855 AYAs with invasive cancer diagnosed in California 2001-2011 were obtained from the California Cancer Registry. We used multivariable Cox proportional hazards regression to estimate overall survival.ResultsAssociations of public or no insurance with greater risk of death were observed for 11 of 12 AYA cancers examined. Compared to Whites, Blacks experienced greater risk of death, regardless of age or insurance, while greater risk of death among Hispanics and Asians was more apparent for younger AYAs and for those with private/military insurance. More pronounced neighborhood SES disparities in survival were observed among AYAs with private/military insurance, especially among younger AYAs.ConclusionsLacking or having public insurance was consistently associated with shorter survival, while disparities according to race/ethnicity and neighborhood SES were greater among AYAs with private/military insurance. While health insurance coverage associates with survival, remaining racial/ethnic and socioeconomic disparities among AYAs with cancer suggest additional social factors also need consideration in intervention and policy development.

IntroductionIt is increasingly essential for medical researchers to be literate in statistics, but the requisite degree of literacy is not the same for every statistical competency in translational research. Statistical competency can range from 'fundamental' (necessary for all) to 'specialized' (necessary for only some). In this study, we determine the degree to which each competency is fundamental or specialized.MethodsWe surveyed members of 4 professional organizations, targeting doctorally trained biostatisticians and epidemiologists who taught statistics to medical research learners in the past 5 years. Respondents rated 24 educational competencies on a 5-point Likert scale anchored by 'fundamental' and 'specialized.'ResultsThere were 112 responses. Nineteen of 24 competencies were fundamental. The competencies considered most fundamental were assessing sources of bias and variation (95%), recognizing one's own limits with regard to statistics (93%), identifying the strengths, and limitations of study designs (93%). The least endorsed items were meta-analysis (34%) and stopping rules (18%).ConclusionWe have identified the statistical competencies needed by all medical researchers. These competencies should be considered when designing statistical curricula for medical researchers and should inform which topics are taught in graduate programs and evidence-based medicine courses where learners need to read and understand the medical research literature.

BackgroundMedication prior authorization (PA) is a commonly occurring requirement, particularly for medications used for rare conditions. Based on standard definitions, cancer and many blood disorders affecting children are rare. The study aims were to describe the relative frequency of PA requests and their association with payers and medications in order to identify opportunities to improve system efficiency.ProcedureRequests for medication PA were logged prospectively for patients seen at a single institution over a 7-month period. Period prevalence was used to estimate the relative frequency of PA requests. Descriptive statistics summarized the relationship among payers, medications, and approvals relative to the frequency of PA requests.ResultsFor the study duration of 150 clinic days, there were 5,583 patient visits. A total of 142 medication PA requests were received resulting in a period prevalence rate of 2.5% patient visits. Of the 137 medication PA requests with available outcome data, 135 (98.5%) were ultimately approved with additional provider efforts. The median clinic staff time spent per request was 46 min with an interquartile range of 25-80 min. There was striking process heterogeneity among different payers.ConclusionVirtually no medication PA request in pediatric hematology and oncology (PHO) leads to alterations in care. Medication utilization management strategies in PHO fail to provide benefits reported in other areas of medicine and have unmeasured negative effects on timeliness of care and parenteral psychological/emotional health. There is opportunity for increasing efficiency through payer and provider collaboration on the creation of prescribing standards for PHO patients.

Purpose Optimal assessment methods and criteria for reporting hearing outcomes in children who receive treatment with cisplatin are uncertain. The objectives of our study were to compare different ototoxicity classification systems, to evaluate the feasibility of including otoacoustic emissions and extended high frequency audiometry, and to evaluate a central review mechanism for audiologic results for cisplatin-treated children in the cooperative group setting. Patients and Methods Eligible participants were 1 to 30 years, with planned cisplatin-containing treatment. Hearing evaluations were conducted at baseline, before each cisplatin cycle, and at the end of therapy. Audiologic results were assessed and graded by the testing audiologist and by two central review audiologists using the American Speech-Language-Hearing Association Ototoxicity Criteria (ASHA), Common Terminology Criteria for Adverse Events, version 3.0 (CTCAE), and Brock Ototoxicity Grades (Brock). One central reviewer also used the International Society of Pediatric Oncology Ototoxicity Scale (SIOP). Results At the end of treatment, the prevalence of any degree of ototoxicity ranged from 40% to 56%, and severe ototoxicity ranged from 7% to 22%. Compared with CTCAE, SIOP detected significantly more ototoxicity ( P = .004), whereas Brock criteria detected significantly fewer patients with any or severe ototoxicity ( P < .001 for both). SIOP detected ototoxicity earlier than did the other scales. Agreement between the central reviewers and the institutional audiologist was almost perfect for ASHA and Brock, whereas the poorest agreement occurred with CTCAE. Conclusion The SIOP scale may be superior to ASHA, Brock, and CTCAE scales for classifying ototoxicity in pediatric patients who were treated with cisplatin. Future studies should evaluate inter-rater reliability of the SIOP scale.

PurposeTo learn the size, composition, and scholarly output of biostatistics, epidemiology, and research design (BERD) units in U.S. academic health centers (AHCs).MethodEach year for four years, the authors surveyed all BERD units in U.S. AHCs that were members of the Clinical and Translational Science Award (CTSA) Consortium. In 2010, 46 BERD units were surveyed; in 2011, 55; in 2012, 60; and in 2013, 61.ResultsResponse rates to the 2010, 2011, 2012, and 2013 surveys were 93.5%, 98.2%, 98.3%, and 86.9%, respectively. Overall, the size of BERD units ranged from 3 to 86 individuals. The median FTE in BERD units remained similar and ranged from 3.0 to 3.5 FTEs over the years. BERD units reported more availability of doctoral-level biostatisticians than doctoral-level epidemiologists. In 2011, 2012, and 2013, more than a third of BERD units provided consulting support on 101 to 200 projects. A majority of BERD units reported that between 25% and 75% (in 2011) and 31% to 70% (in 2012) of their consulting was to junior investigators. More than two-thirds of BERD units reported their contributions to the submission of 20 or more non-BERD grant or contract applications annually. Nearly half of BERD units reported 1 to 10 manuscripts submitted annually with a BERD practitioner as the first or corresponding author.ConclusionsThe findings regarding BERD units provide a benchmark against which to compare BERD resources and may be particularly useful for institutions planning to develop new units to support programs such as the CTSA.

BackgroundSodium thiosulfate is an antioxidant shown in preclinical studies in animals to prevent cisplatin-induced hearing loss with timed administration after cisplatin without compromising the antitumour efficacy of cisplatin. The primary aim of this study was to assess sodium thiosulfate for prevention of cisplatin-induced hearing loss in children and adolescents.MethodsACCL0431 was a multicentre, randomised, open-label, phase 3 trial that enrolled participants at 38 participating Children's Oncology Group hospitals in the USA and Canada. Eligible participants aged 1-18 years with newly diagnosed cancer and normal audiometry were randomly assigned (1:1) to receive sodium thiosulfate or observation (control group) in addition to their planned cisplatin-containing chemotherapy regimen, using permuted blocks of four. Randomisation was initially stratified by age and duration of cisplatin infusion. Stratification by previous cranial irradiation was added later as a protocol amendment. The allocation sequence was computer-generated centrally and concealed to all personnel. Participants received sodium thiosulfate 16 g/m2 intravenously 6 h after each cisplatin dose or observation. The primary endpoint was incidence of hearing loss 4 weeks after final cisplatin dose. Hearing was measured using standard audiometry and reviewed centrally by audiologists masked to allocation using American Speech-Language-Hearing Association criteria but treatment was not masked for participants or clinicians. Analysis of the primary endpoint was by modified intention to treat, which included all randomly assigned patients irrespective of treatment received but restricted to those assessable for hearing loss. Enrolment is complete and this report represents the final analysis. This trial is registered with ClinicalTrials.gov, number NCT00716976.FindingsBetween June 23, 2008, and Sept 28, 2012, 125 eligible participants were randomly assigned to either sodium thiosulfate (n=61) or observation (n=64). Of these, 104 participants were assessable for the primary endpoint (sodium thiosulfate, n=49; control, n=55). Hearing loss was identified in 14 (28·6%; 95% CI 16·6-43·3) participants in the sodium thiosulfate group compared with 31 (56·4%; 42·3-69·7) in the control group (p=0·00022). Adjusted for stratification variables, the likelihood of hearing loss was significantly lower in the sodium thiosulfate group compared with the control group (odds ratio 0·31, 95% CI 0·13-0·73; p=0·0036). The most common grade 3-4 haematological adverse events reported, irrespective of attribution, were neutropenia (117 [66%] of 177 participant cycles in the sodium thiosulfate group vs 145 [65%] of 223 in the control group), whereas the most common non-haematological adverse event was hypokalaemia (25 [17%] of 147 vs 22 [12%] of 187). Of 194 serious adverse events reported in 26 participants who had received sodium thiosulfate, none were deemed probably or definitely related to sodium thiosulfate; the most common serious adverse event was decreased neutrophil count: 26 episodes in 14 participants.InterpretationSodium thiosulfate protects against cisplatin-induced hearing loss in children and is not associated with serious adverse events attributed to its use. Further research is needed to define the appropriate role for sodium thiosulfate among emerging otoprotection strategies.FundingUS National Cancer Institute.

South Texas currently has the highest incidence of hepatocellular carcinoma (HCC) in the United States, a disease that disproportionately affects Latino populations in the region. Aflatoxin B1 (AFB1) is a potent liver carcinogen that has been shown to be present in a variety of foods in the United States, including corn and corn products. Importantly, it is a dietary risk factor contributing to a higher incidence of HCC in populations frequently consuming AFB1-contaminated diets. In a randomised double-blind placebo controlled trial, we evaluated the effects of a 3-month administration of ACCS100 (refined calcium montmorillonite clay) on serum AFB1-lysine adduct (AFB-Lys) level and serum biochemistry in 234 healthy men and women residing in Bexar and Medina counties, Texas. Participants recruited from 2012 to 2014 received either a placebo, 1.5 g or 3 g ACCS100 each day for 3 months, and no treatment during the fourth month. Adverse event rates were similar across treatment groups and no significant differences were observed for serum biochemistry and haematology parameters. Differences in levels of AFB-Lys at 1, 3 and 4 months were compared between placebo and active treatment groups. Although serum AFB-Lys levels were decreased by month 3 for both treatment groups, the low dose was the only treatment that was significant (p = 0.0005). In conclusion, the observed effect in the low-dose treatment group suggests that the use of ACCS100 may be a viable strategy to reduce dietary AFB1 bioavailability during aflatoxin outbreaks and potentially in populations chronically exposed to this carcinogen.

BackgroundBreast and colorectal cancers are common cancers for which genetic risk assessment and counseling are available. However, these services are often limited to metropolitan areas and are not readily accessible to underserved populations. Moreover, ethnic and racial disparities present additional obstacles to identifying and screening high-risk individuals and have a bearing on treatment outcomes.ObjectiveTo provide cancer genetic risk assessment and counseling through telemedicine to the remote, underserved primarily Hispanic population of the Texas-Mexico border region.MethodsProgram participants were mailed a questionnaire to assess their satisfaction with the program so that we could determine the acceptability of video-teleconferencing for cancer risk assessment.ResultsThe overall level of satisfaction with the program was very high, demonstrating the acceptability of a cancer genetic risk assessment program that relied on telemedicine to reach and underserved minority community.LimitationsDelivery model requires the availability of and access to communication technologies; trained staff are needed at remote sites for sample collection and patient handling.ConclusionVideo-teleconferencing is an acceptable method of providing cancer risk assessment in a remote, underserved population.

PurposeStagnant outcomes for adolescents and young adults (AYAs; 15 to 39 years old) with cancer are partly attributed to poor enrollment onto clinical trials. The National Cancer Institute (NCI) Community Clinical Oncology Program (CCOP) was developed to improve clinical trial participation in the community setting, where AYAs are most often treated. Further, many CCOP sites had pediatric and medical oncologists with collaborative potential for AYA recruitment and care. For these reasons, we hypothesized that CCOP sites enrolled proportionately more AYAs than non-CCOP sites onto Children's Oncology Group (COG) trials.MethodsFor the 10-year period 2004 through 2013, the NCI Division of Cancer Prevention database was queried to evaluate enrollments into relevant COG studies. The proportional enrollment of AYAs at CCOP and non-CCOP sites was compared and the change in AYA enrollment patterns assessed. All sites were COG member institutions.ResultsAlthough CCOP sites enrolled a higher proportion of patients in cancer control studies than non-CCOP sites (3.5% v 1.8%; P < .001), they enrolled a lower proportion of AYAs (24.1% v 28.2%, respectively; P < .001). Proportional AYA enrollment at CCOP sites decreased during the intervals 2004 through 2008 and 2009 through 2013 (26.7% v 21.7%; P < .001).ConclusionDespite oncology practice settings that might be expected to achieve otherwise, CCOP sites did not enroll a larger proportion of AYAs in clinical trials than traditional COG institutions. Our findings suggest that the CCOP (now the NCI Community Oncology Research Program) can be leveraged for developing targeted interventions for overcoming AYA enrollment barriers.

p53 activation is a primary mechanism underlying pathological responses to DNA damaging agents such as chemotherapy and radiotherapy. Our recent animal studies showed that low dose arsenic (LDA)-induced transient p53 inhibition selectively protected normal tissues from chemotherapy-induced toxicity. Study objectives were to: 1) define the lowest safe dose of arsenic trioxide that transiently blocks p53 activation in patients and 2) assess the potential of LDA to decrease hematological toxicity from chemotherapy. Patients scheduled to receive minimum 4 cycles of myelosuppressive chemotherapy were eligible. For objective 1, dose escalation of LDA started at 0.005 mg/kg/day for 3 days. This dose satisfied objective 1 and was administered before chemotherapy cycles 2, 4, and 6 for objective 2. p53 level in peripheral lymphocytes was measured on day 1 of each cycle by ELISA assay. Chemotherapy cycles 1, 3, and 5 served as the baseline for the subsequent cycles of 2, 4, and 6 respectively. If p53 level for the subsequent cycle was lower (or higher) than the baseline cycle, p53 was defined as "suppressed" (or "activated") for the pair of cycles. Repeated measures linear models of CBC in terms of day, cycle, p53 activity and interaction terms were used. Twenty-six patients treated with 3 week cycle regimens form the base of analyses. The mean white blood cell, hemoglobin and absolute neutrophil counts were significantly higher in the "suppressed" relative to the "activated" group. These data support the proof of principle that suppression of p53 could lead to protection of bone marrow in patients receiving chemotherapy. This trial is registered in ClinicalTrials.gov. Identifier: NCT01428128.