Individual and cumulative health afflictions are associated with greater impairment in physical and mental function in former professional American style football players.

BACKGROUND: Former American style football players (ASF players) have recognized health concerns associated with prior sport participation. It remains unknown whether categorizations of current health conditions, referred to in this report as afflictions (conceptually framed as neurocognitive, cardiovascular, cardiometabolic, sleep apnea, and chronic pain) are associated with physical and mental function. OBJECTIVE: To evaluate the association of afflictions to physical and mental function. It was hypothesized that former National Football League players with any affliction would have worse function compared to unafflicted participants. It was anticipated that multiple afflictions would result in cumulative loss of function. DESIGN: Cross-sectional retrospective design. SETTING: Academic medical multisite hospital system. PARTICIPANTS: A total of 3913 of 15,611 former ASF players who played professionally from 1960 to 2019 (response rate 25%). Assessment of Risk Factors Self-report survey. MAIN OUTCOME MEASURES: Each participant completed the Patient Reported Outcomes Measurement Information System (PROMIS) Global Health Scale and Physical Function questionnaires. Responses were used to generate two physical function and one mental function subscale scores. Raw scores were converted to T-scores categorized as impaired (T-score < 40) or unimpaired (T-score ≥ 40). Primary analyses measured the association of affliction to function (impaired or unimpaired). RESULTS: After adjusting for confounders (age, race, position, number of seasons, age of first exposure to football, alcohol use, smoking history, and current body mass index), each affliction was associated with reduced physical function on the Global physical function subscale (risk ratio [RR] = 1.23-2.45, all P < .005), physical function scale (RR = 1.24-2.75, all P < .01), and mental function scale (RR = 1.34-2.87, all P < .001), except that cardiovascular affliction was not associated with mental function (RR = 1.15, P = .15). The lowest functional measures were observed in those afflicted by chronic pain. Cumulative afflictions were associated with worse function. CONCLUSIONS: Afflictions are associated with cumulative reduction of function. Research evaluating how afflictions interact may help elucidate mechanisms for illness and develop interventions to optimize function.

Development of a Coronavirus Disease 2019 (COVID-19) Application Ontology for the Accrual to Clinical Trials (ACT) network.

Clinical data networks that leverage large volumes of data in electronic health records (EHRs) are significant resources for research on coronavirus disease 2019 (COVID-19). Data harmonization is a key challenge in seamless use of multisite EHRs for COVID-19 research. We developed a COVID-19 application ontology in the national Accrual to Clinical Trials (ACT) network that enables harmonization of data elements that are critical to COVID-19 research. The ontology contains over 50 000 concepts in the domains of diagnosis, procedures, medications, and laboratory tests. In particular, it has computational phenotypes to characterize the course of illness and outcomes, derived terms, and harmonized value sets for severe acute respiratory syndrome coronavirus 2 laboratory tests. The ontology was deployed and validated on the ACT COVID-19 network that consists of 9 academic health centers with data on 14.5M patients. This ontology, which is freely available to the entire research community on GitHub at https://github.com/shyamvis/ACT-COVID-Ontology, will be useful for harmonizing EHRs for COVID-19 research beyond the ACT network.

Development of a COVID-19 Application Ontology for the ACT Network.

Clinical data networks that leverage large volumes of data in electronic health records (EHRs) are significant resources for research on coronavirus disease 2019 (COVID-19). Data harmonization is a key challenge in seamless use of multisite EHRs for COVID-19 research. We developed a COVID-19 application ontology in the national Accrual to Clinical Trials (ACT) network that enables harmonization of data elements that that are critical to COVID-19 research. The ontology contains over 50,000 concepts in the domains of diagnosis, procedures, medications, and laboratory tests. In particular, it has computational phenotypes to characterize the course of illness and outcomes, derived terms, and harmonized value sets for SARS-CoV-2 laboratory tests. The ontology was deployed and validated on the ACT COVID-19 network that consists of nine academic health centers with data on 14.5M patients. This ontology, which is freely available to the entire research community on GitHub at https://github.com/shyamvis/ACT-COVID-Ontology, will be useful for harmonizing EHRs for COVID-19 research beyond the ACT network.

Modifiable Risk Factors for Poor Cognitive Function in Former American-Style Football Players: Findings from the Harvard Football Players Health Study.

Recent attention to consequences of head trauma among former professional American-style football players has increased the likelihood that former players and their healthcare providers attribute neurocognitive effects to these exposures. In addition to head trauma, however, many potentially modifiable risk factors are associated with cognitive impairment. We examined the association of self-reported risk factors for cognitive impairment (e.g., cardiovascular health, sleep, pain, depression, anxiety, smoking, physical impairment, and physical activity) with cognition-related quality of life, measured by the Quality of Life in Neurological Disorders, Applied Cognition-General Concerns (Neuro-QOL) among 3803 former National Football League (NFL) players. We examined the prevalence of risk factors among men who had experienced a high number of concussion symptoms during playing years, comparing men with good current cognition-related QOL, the "healthy concussed," to men with poor cognition-related QOL, the "unhealthy concussed." Physical functioning, pain, depression, and anxiety were very strongly associated with poor cognitive-related QOL (risk ratio range, 2.21-2.70, p < 0.0001 for all). Short sleep duration and low physical activity were also strongly associated (RR = 1.69 and 1.57, respectively, p < 0.0001 for both). The largest differences between healthy and unhealthy concussed were in chronic pain (72.0% vs. 21.2%), depressive symptoms (50.3% vs. 6.3%), anxiety symptoms (53.4% vs. 11.6%), and physical impairment (52.4% vs. 12.5%). Substantial differences also existed in prevalence of sleep apnea, short sleep duration, high-intensity exercise, weight training, high blood pressure, and body mass index ≥35 kg/m2 (all differences >10 percentage points). We identified cognitive risk factors, including chronic pain, mood problems, sleep problems, obesity, and lack of exercise, that were commonly present in former football players with cognition-related impairment. Better treatment for these factors may reduce cognitive problems in this population.

Premortem Chronic Traumatic Encephalopathy Diagnoses in Professional Football.

OBJECTIVE: American-style football (ASF) has gained attention because of possible links between repetitive head injury and neurodegenerative diseases. Although postmortem pathologic changes consistent with chronic traumatic encephalopathy (CTE) have been reported in ASF players, there are currently no established premortem diagnostic criteria for CTE. Nevertheless, presented with symptoms of cognitive impairment, clinicians treating former players may be inclined to suggest CTE without a thorough exploration of comorbid factors that demonstrate similar clinical phenotypes to putative CTE. METHODS: A survey of 3,913 former ASF players aged 24 to 89 was conducted for those who responded by March 2019. RESULTS: Despite being a postmortem diagnosis, 108 players (2.8%) self-reported clinician-diagnosed CTE. The percentage of players under age 60 years reporting a CTE diagnosis was 2.3% versus 3.7% in participants age 60 or older. Comorbidities in participants self-reporting CTE were significantly more common, including sleep apnea, hypercholesterolemia, obesity, indicators of past or current depression, hypertension, prescription pain medication use, heart conditions, and low testosterone when compared to non-CTE respondents. Patterns of reporting for obesity, hypertension, heart conditions, or hypercholesterolemia differed between older and younger participants. Cognitive impairment symptoms were significantly higher in participants self-reporting CTE. INTERPRETATION: Some former professional football players have been clinically diagnosed with CTE, a postmortem condition. Comorbidities that can affect cognition were associated with CTE diagnoses in both older and younger players. Although underlying neuropathology cannot be ruled out, treatable conditions should be explored in former athletes demonstrating CTE-linked clinical phenotypes or symptoms as a means of improving cognitive health in these patients. ANN NEUROL 2020 ANN NEUROL 2020;88:106-112.

Self-Reported Cognitive Function and Mental Health Diagnoses among Former Professional American-Style Football Players.

Clinical practice strongly relies on patients' self-report. Former professional American-style football players are hesitant to seek help for mental health problems, but may be more willing to report cognitive symptoms. We sought to assess the association between cognitive symptoms and diagnosed mental health problems and quality of life among a cohort of former professional players. In a cross-sectional design, we assessed self-reported cognitive function using items from the Quality of Life in Neurological Disorders (Neuro-QOL) Item Bank. We then compared mental health diagnoses and quality of life, assessed by items from the Patient-Reported Outcome Measurement Information System (PROMIS®), between former professional players reporting daily problems in cognitive function and former players not reporting daily cognitive problems. Of the 3758 former professional players included in the analysis, 40.0% reported daily problems due to cognitive dysfunction. Former players who reported daily cognitive problems were more likely to also report depression (18.0% vs. 3.3%, odds ratio [OR] = 6.42, 95% confidence interval [CI] [4.90-8.40]) and anxiety (19.1% vs. 4.3%, OR = 5.29, 95% CI [4.14-6.75]) than those without daily cognitive problems. Further, former players reporting daily cognitive problems were more likely to report memory loss and attention deficit(/hyperactivity) disorder and poorer general mental health, lower quality of life, less satisfaction with social activities and relationships, and more emotional problems. These findings highlight the potential of an assessment of cognitive symptoms for identifying former players with mental health, social, and emotional problems.

Scale-up of the Accrual to Clinical Trials (ACT) network across the Clinical and Translational Science Award Consortium: a mixed-methods evaluation of the first 18 months.

INTRODUCTION: The Clinical and Translational Science Award (CTSA) Program is a Consortium of nearly 60 academic medical research centers across the USA and a natural network for evaluating the spread and uptake of translational research innovation across the Consortium. METHODS: Dissemination of the Accrual to Clinical Trials (ACT) Network, a federated clinical informatics data network for population-based cohort discovery, began January 2018 across the Consortium. Diffusion of innovation theory guided dissemination design and evaluation. Mixed-methods assessed the spread and uptake across the Consortium through July 1, 2019 (n = 48 CTSAs). Methods included prospective time activity tracking (Kaplan-Meier curves), and survey and qualitative interviews. RESULTS: Within 18 months, nearly 80% of CTSAs had joined the data network and two-thirds of CTSAs achieving technical readiness had initiated launch to local clinical investigators. Over 10,000 ACT Network queries are projected for 2019; and by 2020, nearly all CTSAs will have joined the network. Median time-from-technical-readiness-to-local-launch was 154 days (interquartile range: 87-225 days]. Quality improvement processes reduced time-to-launch by 35.2% (64 days, p = 0.0036). Lessons learned include: (1) conceptualize dissemination as two-stage adoption demonstrating value for both CTSA hub service providers and clinical investigators; (2) include institutional trial into dissemination strategies so CTSA hubs can refine internal workflows and gather local user feedback endorsement; (3) embrace designing-for-dissemination during technology development; and (4) sustain adaptive dissemination and customer relationship management to keep CTSA hubs and users engaged. CONCLUSIONS: Scale-up and spread of the ACT Network provides lessons learned for others disseminating innovation across the CTSA Consortium. The Network is primed for embedded implementation research.

The SMART IRB platform: A national resource for IRB review for multisite studies.

Single institutional review board (IRB) review of multisite research increased in frequency over a decade ago with a proliferation of master IRB reliance agreements supporting statewide and regional consortia and disease- and population-specific networks. Although successful, the increasing number of agreements presented significant challenges and illuminated potential benefits of a single, nationwide agreement. Anticipated changes in federal regulations highlighted the need to systematize and simplify IRB reliance. To address these challenges, the NIH National Center for Advancing Translational Sciences funded a project to establish a national IRB reliance network that would support national adoption of single IRB (sIRB) review. The Streamlined, Multisite, Accelerated Resources for Trials (SMART) IRB Platform launched in July 2016 to facilitate dissemination, adoption, and implementation of a collaboratively developed master IRB reliance agreement and supportive tools and resources. More than 580 institutions have joined SMART IRB's Master Common Reciprocal Institutional Review Board Authorization Agreement and begun using the SMART IRB platform to support sIRB arrangements. Here, we describe the tenets of the agreement and operational benefits and challenges of its use. SMART IRB's early success affirms the utility of collaborative, flexible, and centralized approaches to supporting sIRB review while highlighting the need for further national harmonization.

Association of Concussion Symptoms With Testosterone Levels and Erectile Dysfunction in Former Professional US-Style Football Players.

Importance: Small studies suggest that head trauma in men may be associated with low testosterone levels and sexual dysfunction through mechanisms that likely include hypopituitarism secondary to ischemic injury and pituitary axonal tract damage. Athletes in contact sports may be at risk for pituitary insufficiencies or erectile dysfunction (ED) because of the high number of head traumas experienced during their careers. Whether multiple symptomatic concussive events are associated with later indicators of low testosterone levels and ED is unknown. Objective: To explore the associations between concussion symptom history and participant-reported indicators of low testosterone levels and ED. Design, Setting, and Participants: This cross-sectional study of former professional US-style football players was conducted in Boston, Massachusetts, from January 2015 to March 2017. Surveys on past football exposures, demographic factors, and current health conditions were sent via electronic and postal mail to participants within and outside of the United States. Analyses were conducted in Boston, Massachusetts; the data analysis began in March 2018 and additional analyses were performed through June 2019. Of the 13 720 male former players eligible to enroll who were contacted, 3506 (25.6%) responded. Exposures: Concussion symptom score was calculated by summing the frequency with which participants reported 10 symptoms, such as loss of consciousness, disorientation, nausea, memory problems, and dizziness, at the time of football-related head injury. Main Outcomes and Measures: Self-reported recommendations or prescriptions for low testosterone or ED medication served as indicators for testosterone insufficiency and ED. Results: In 3409 former players (mean [SD] age, 52.5 [14.1] years), the prevalence of indicators of low testosterone levels and ED was 18.3% and 22.7%, respectively. The odds of reporting low testosterone levels or ED indicators were elevated for previously established risk factors (eg, diabetes, sleep apnea, and mood disorders). Models adjusted for demographic characteristics, football exposures, and current health factors showed a significant monotonically increasing association of concussion symptom score with the odds of reporting the low testosterone indicator (highest vs lowest quartile, odds ratio, 2.39; 95% CI, 1.79-3.19; P < .001). The ED indicator showed a similar association (highest quartile vs lowest, odds ratio, 1.72; 95% CI, 1.30-2.27; P < .001). Conclusions and Relevance: Concussion symptoms at the time of injury among former football players were associated with current participant-reported low testosterone levels and ED indicators. These findings suggest that men with a history of head injury may benefit from discussions with their health care clinicians regarding testosterone deficiency and sexual dysfunction.

Exposure to American Football and Neuropsychiatric Health in Former National Football League Players: Findings From the Football Players Health Study.

BACKGROUND: Former American football players have a higher prevalence of cognitive impairment than that of the US general population. It remains unknown what aspects of playing football are associated with neuropsychiatric outcomes. HYPOTHESIS: It was hypothesized that seasons of professional football, playing position, and experience of concussions were associated with cognition-related quality of life (QOL) and indicators of depression and anxiety. STUDY DESIGN: Descriptive epidemiology study. METHODS: The authors examined whether seasons of professional football, playing position, and experience of concussions, as measured by self-report of 10 symptoms, were associated with cognition-related QOL and indicators of depression and anxiety in a cross-sectional survey conducted 2015 to 2017. Cognition-related QOL was measured by the short form of the Quality of Life in Neurological Disorders: Applied Cognition-General Concerns. The Patient Health Questionnaire-4 measured depression and anxiety symptoms. Of 13,720 eligible men with apparently valid contact information, 3506 players returned a questionnaire at the time of this analysis (response rate = 25.6%). RESULTS: Seasons of professional play (risk ratio [RR] per 5 seasons = 1.19, 95% CI = 1.06-1.34) and playing position were associated with cognition-related QOL. Each 5 seasons of play was associated with 9% increased risk of indicators of depression at borderline statistical significance (P = .05). When compared with former kickers, punters, and quarterbacks, men who played any other position had a higher risk of poor cognition-related QOL, depression, and anxiety. Concussion symptoms were strongly associated with poor cognition-related QOL (highest concussion quartile, RR = 22.3, P < .001), depression (highest quartile, RR = 6.0, P < .0001), and anxiety (highest quartile, RR = 6.4, P < .0001), even 20 years after last professional play. CONCLUSION: The data suggest that seasons of play and playing position in the NFL are associated with lasting neuropsychiatric health deficits. Additionally, poor cognition-related QOL, depression, and anxiety appear to be associated with concussion in the long term.

The Football Players' Health Study at Harvard University: Design and objectives.

The Football Players Health Study at Harvard University (FPHS) is a unique transdisciplinary, strategic initiative addressing the challenges of former players' health after having participated in American style football (ASF). The whole player focused FPHS is designed to deepen understanding of the benefits and risks of participation in ASF, identify risks that are potentially reversible or preventable, and develop interventions or approaches to improve the health and wellbeing of former players. We are recruiting and following a cohort of former professional ASF players who played since 1960 (current n = 3785). At baseline, participants complete a self-administered standardized questionnaire, including initial reporting of exposure history and physician-diagnosed health conditions. Additional arms of the initiative are addressing targeted studies, including promising primary, secondary, and tertiary interventions; extensive in-person clinical phenotyping, and legal and ethical concerns of the play. This paper describes the components of the FPHS studies undertaken and completed thus far, as well as those studies currently underway or planned for the near future. We present our initiatives herein as a potential paradigm of one way to proceed (acknowledging that it is not the only way). We share what we have learned so that it may be useful to others, particularly in regard to trying to make professional sports meet the needs of multiple stakeholders ranging from players to owners, to fans, and possibly even to parents making decisions for their children.

Multisystem afflictions in former National Football League players.

BACKGROUND: The long-term health consequences of participation in American style football (ASF) are not well understood. METHODS: We conducted a retrospective cohort study of men who had played in the NFL after 1960. Participants were studied using a standardized self-administered questionnaire designed to determine both the exposure history to ASF and the prevalence of chronic pain, sleep apnea, cardiometabolic disease, and neurocognitive impairment. Logistic regression and negative binomial regression models were used to assess associations between age, ethnicity, body-mass index during professional football career, field position, and football career duration with individual and multiple afflictions. RESULTS: In this cohort of former NFL players (n = 3745), approximately one quarter of the eligible former players (27%) reported two or more medical afflictions (chronic pain, cardiometabolic disease, sleep apnea, or neurocognitive impairment). Career duration was significantly associated with an increase in the number of comorbidities. Age, race, and body-mass index were associated with all affliction categories, other than neurocognitive impairment, which was similarly prevalent in middle-aged players and older players. Earlier age when first playing the sport was protective against cardiometabolic affliction. CONCLUSIONS: Former NFL players report significant combinations of cross-system afflictions. Future work will be required to determine mechanistic underpinnings. However, attention to the whole player, rather than specific organ systems seems critical to improve long-term health outcomes in former ASF professional athletes.

Mortality Among Professional American-Style Football Players and Professional American Baseball Players.

Importance: Studies of American-style football players have suggested lower overall mortality rates compared with general populations, but with possibly increased neurodegenerative mortality. However, comparisons with general populations can introduce bias. This study compared mortality between US National Football League (NFL) and US Major League Baseball (MLB) players, a more appropriate comparison group of professional athletes. Objective: To compare all-cause and cause-specific mortality between NFL and MLB players. Design, Setting, and Participants: In this retrospective cohort study, the setting was US mortality from January 1, 1979, through December 31, 2013. The dates of analysis were January 2016 to April 2019. Participants were 3419 NFL and 2708 MLB players with at least 5 playing seasons. Exposures: Participation in the NFL compared with the MLB. Main Outcomes and Measures: Vital status and causes of death from the National Death Index from 1979 through 2013 were obtained. Cox proportional hazards regression models using age as the timescale were used to calculate hazard ratios (HRs) and 95% CIs to examine all-cause and cause-specific mortality among NFL players compared with MLB players, adjusted for race and decade of birth. Results: By the end of follow-up, there were 517 deaths (mean [SD] age, 59.6 [13.2] years) in the NFL cohort and 431 deaths (mean [SD] age, 66.7 [12.3] years) in the MLB cohort. Cardiovascular and neurodegenerative conditions, respectively, were noted as underlying or contributing causes in 498 and 39 deaths in the NFL and 225 and 16 deaths in the MLB. Compared with MLB players, NFL players had significantly elevated rates of all-cause (HR, 1.26; 95% CI, 1.10-1.44), cardiovascular disease (HR, 2.40; 95% CI, 2.03-2.84), and neurodegenerative disease (HR, 2.99; 95% CI, 1.64-5.45) mortality. Comparing hypothetical populations of 1000 NFL and 1000 MLB players followed up to age 75 years, there would be an excess 21 all-cause deaths among NFL players, as well as 77 and 11 more deaths with underlying or contributing causes that included cardiovascular and neurodegenerative conditions, respectively. Conclusions and Relevance: This study found that NFL players had elevated all-cause, cardiovascular, and neurodegenerative mortality rates compared with MLB players, although the absolute number of excess neurodegenerative deaths was still small. Factors that vary across these sports (eg, body habitus and head trauma) as opposed to those common across sports (eg, physical activity) could underlie the differences.

Defining Exposures in Professional Football: Professional American-Style Football Players as an Occupational Cohort.

Studies of professional American football players have shown that football-related activities lead to acute injuries and may have long-term adverse health outcomes including osteoarthritis, neurocognitive impairment, and cardiovascular disease. However, the full complement of what constitutes professional football exposure has yet to be effectively articulated. Most likely, professional football exposure encompasses a multifaceted array of experiences including head impacts and joint stresses, long-term pain medication use, dietary restrictions, and strenuous training regimens. To study the health of professional American football players, characterizing the group as an occupational cohort and taking advantage of methods established within the discipline of occupational epidemiology may be beneficial. We conducted a narrative review of existing football research, occupational epidemiological methods papers, and occupational medicine studies. Here we describe the traditional occupational epidemiological approach to assessing exposure in a novel cohort and show how this framework could be implemented in studies of professional football players. In addition, we identify the specific challenges associated with studying an elite athletic occupational group, including the healthy worker effect and other types of selection and information biases, and explore these in the context of existing studies of football-related health. The application of well-established occupational epidemiological methods to professional football players may yield new insights into the effects of playing exposure and may provide opportunities for interventions to reduce harm.

Accrual to Clinical Trials (ACT): A Clinical and Translational Science Award Consortium Network.

The Accrual to Clinical Trials (ACT) network is a federated network of sites from the National Clinical and Translational Science Award (CTSA) Consortium that has been created to significantly increase participant accrual to multi-site clinical trials. The ACT network represents an unprecedented collaboration among diverse CTSA sites. The network has created governance and regulatory frameworks and a common data model to harmonize electronic health record (EHR) data, and deployed a set of Informatics for Integrating Biology and the Bedside (i2b2) data repositories that are linked by the Shared Health Research Information Network (SHRINE) platform. It provides investigators the ability to query the network in real time and to obtain aggregate counts of patients who meet clinical trial inclusion and exclusion criteria from sites across the United States. The ACT network infrastructure provides a basis for cohort discovery and for developing new informatics tools to identify and recruit participants for multi-site clinical trials.

Relation of Anterior Cruciate Ligament Tears to Potential Chronic Cardiovascular diseases.

We have enrolled a cohort of former National Football League players (n = 3,506) who played since 1960 to assess potential long term health consequences associated with participating in the sport. Each participant has completed a self-administered questionnaire including reporting of physician-diagnosed health conditions. One of the early assessments was to evaluate whether anterior cruciate ligament (ACL) tears were associated with later life co-morbidities, including cardiovascular effects. We used Cox proportional hazards to estimate hazard ratios (HR) for joint replacement surgeries, myocardial infarction, sleep apnea, arthritis, dementia, and stroke by history of ACL tear during their professional career. For additional outcomes without date of occurrence reported we used logistic regression to estimate odds ratios adjusted for potential confounding variables in all models. After adjusting for covariates, former National Football League players who tore their ACL had approximately a twofold increase in muscular skeletal co-morbidities, including knee joint replacement and arthritis, compared with those without ACL tears. In addition, those with a history of ACL tears also had more than a 50% increased risk of myocardial infarction (HR 1.52; 95% confidence interval 0.97 to 2.38) and a slight increase in sleep apnea (HR 1.15; 95% confidence interval 0.96 to 1.38). ACL tears sustained by athletes may increase the risk of co-morbidities beyond the musculoskeletal system. As there are more than 100,000 ACL reconstructions annually in the United States, our findings could have widespread public health importance if these findings generalize to a population beyond professional football players. In conclusion, enhanced screening for other risk factors for these conditions in patients who have torn their ACL might identify those who could most benefit from prevention strategies.

Weight Gain and Health Affliction Among Former National Football League Players.

BACKGROUND: Professional American-style football players are among the largest athletes across contemporary sporting disciplines. Weight gain during football participation is common, but the health implications of this early-life weight gain remain incompletely understood. We sought to define weight trajectories of former professional American-style football athletes and to establish their relationship with 5 common health afflictions (cardiovascular disease, cardiometabolic disease, neurocognitive impairment, sleep apnea, and chronic pain). METHODS: A health survey was distributed to former National Football League (NFL) players. Former players reported body weight at 4 time points (high school, college, professional, and time of survey response) as well as maximal retirement weight. Logistic regression was used to assess associations between weight gain during football participation and health affliction. RESULTS: In this cohort of former NFL players (n = 3,506, age 53 ± 14 years), mean weight increase from high school to time of survey response was 40 ± 36 pounds, with the majority of weight gain occurring during periods of football participation (high-school-to-college and college-to-professional). The prevalence of health afflictions ranged from 9% (cardiovascular disease) to 28% (chronic pain). Weight gain during football participation was independently associated with risk of multiple later-life health afflictions in models adjusted for football exposure, lifestyle variables, and post-career weight gain. CONCLUSIONS: Early-life weight gain among American-style football athletes is common and is associated with risk of adverse health profiles during later-life. These findings establish football-associated weight gain as a key predictor of post-career health and raise important questions about the central role of targeted weight gain in this population.

Infusion of Alloanergized Donor Lymphocytes after CD34-selected Haploidentical Myeloablative Hematopoietic Stem Cell Transplantation.

Purpose: Allogeneic hematopoietic stem-cell transplantation (HSCT) is a curative treatment for many hematologic cancers. Use of haploidentical (mismatched) donors increases HSCT availability but is limited by severe graft-versus-host disease (GvHD) and delayed immune reconstitution. Alloanergization of donor T cells is a simple approach to rebuild immunity while limiting GvHD after haploidentical HSCT, but the optimal T-cell dose and impact on immune reconstitution remain unknown.Patients and Methods: We performed a multicenter phase I trial of alloanergized donor lymphocyte infusion (aDLI) after CD34-selected myeloablative haploidentical HSCT. The primary aim was feasibility and safety with secondary aims of assessing the less frequently addressed issue of impact on immune reconstitution.Results: Nineteen patients with high-risk acute leukemia or myelodysplasia were enrolled. Engraftment occurred in 18 of 19 patients (95%). Pre-aDLI, 12 patients (63%) had bacteremia, nine of 17 at-risk patients (53%) reactivated CMV, and one developed acute GvHD. Sixteen patients received aDLI at dose levels 1 (103 T cells/kg, n = 4), 2 (104, n = 8), and 3 (105, n = 4). After aDLI, five patients developed clinically significant acute GvHD, and four of 14 at-risk patients (29%) reactivated CMV. T-cell recovery was significantly greater, and functional virus- and tumor-associated antigen-specific T cells were detectable earlier in patients receiving dose level 2 or 3 versus dose level 1/no aDLI. Alloanergization of donor cells expanded the CD4+ T-regulatory cell frequency within aDLI, which increased further in vivo without impeding expansion of virus- and tumor-associated antigen-specific T cells.Conclusions: These data demonstrate safety and a potential role for aDLI in contributing to immune reconstitution and expanding tolerogenic regulatory T cells in vivo after CD34-selected myeloablative haploidentical HSCT. Clin Cancer Res; 24(17); 4098-109. ©2018 AACR.

Preparedness of the CTSA's structural and scientific assets to support the mission of the National Center for Advancing Translational Sciences (NCATS).

The formation of the National Center for Advancing Translational Sciences (NCATS) brings new promise for moving basic science discoveries to clinical practice, ultimately improving the health of the nation. The Clinical and Translational Science Award (CTSA) sites, now housed with NCATS, are organized and prepared to support in this endeavor. The CTSAs provide a foundation for capitalizing on such promise through provision of a disease-agnostic infrastructure devoted to clinical and translational (C&T) science, maintenance of training programs designed for C&T investigators of the future, by incentivizing institutional reorganization and by cultivating institutional support.