Healthspan and chronic disease burden among young adult and middle-aged male former American-style professional football players.

OBJECTIVE: To examine the relationships between age, healthspan and chronic illness among former professional American-style football (ASF) players. METHODS: We compared age-specific race-standardised and body mass index-standardised prevalence ratios of arthritis, dementia/Alzheimer's disease, hypertension and diabetes among early adult and middle-aged (range 25-59 years) male former professional ASF players (n=2864) with a comparator cohort from the National Health and Nutrition Examination Survey and National Health Interview Survey, two representative samples of the US general population. Age was stratified into 25-29, 30-39, 40-49 and 50-59 years. RESULTS: Arthritis and dementia/Alzheimer's disease were more prevalent among ASF players across all study age ranges (all p<0.001). In contrast, hypertension and diabetes were more prevalent among ASF players in the youngest age stratum only (p<0.001 and p<0.01, respectively). ASF players were less likely to demonstrate intact healthspan (ie, absence of chronic disease) than the general population across all age ranges. CONCLUSION: These data suggest the emergence of a maladaptive early ageing phenotype among former professional ASF players characterised by premature burden of chronic disease and reduced healthspan. Additional study is needed to investigate these findings and their impact on morbidity and mortality in former ASF players and other athlete groups.

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.

Occupational exposure to disinfectants and asthma incidence in U.S. nurses: A prospective cohort study.

BACKGROUND: Exposure to disinfectants among healthcare workers has been associated with respiratory health effects, in particular, asthma. However, most studies are cross-sectional and the role of disinfectant exposures in asthma development requires longitudinal studies. We investigated the association between occupational exposure to disinfectants and incident asthma in a large cohort of U.S. female nurses. METHODS: The Nurses' Health Study II is a prospective cohort of 116 429 female nurses enrolled in 1989. Analyses included 61 539 participants who were still in a nursing job and with no history of asthma in 2009 (baseline; mean age: 55 years). During 277 744 person-years of follow-up (2009-2015), 370 nurses reported incident physician-diagnosed asthma. Occupational exposure was evaluated by questionnaire and a Job-Task-Exposure Matrix (JTEM). We examined the association between disinfectant exposure and subsequent asthma development, adjusted for age, race, ethnicity, smoking status, and body mass index. RESULTS: Weekly use of disinfectants to clean surfaces only (23% exposed) or to clean medical instruments (19% exposed) was not associated with incident asthma (adjusted hazard ratio [95% confidence interval] for surfaces, 1.12 [0.87-1.43]; for instruments, 1.13 [0.87-1.48]). No association was observed between high-level exposure to specific disinfectants/cleaning products evaluated by the JTEM (formaldehyde, glutaraldehyde, bleach, hydrogen peroxide, alcohol quats, or enzymatic cleaners) and asthma incidence. CONCLUSIONS: In a population of late career nurses, we observed no significant association between exposure to disinfectants and asthma incidence. A potential role of disinfectant exposures in asthma development warrants further study among healthcare workers at earlier career stage to limit the healthy worker effect.

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.

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.

Smoking and mortality--beyond established causes.

BACKGROUND: Mortality among current smokers is 2 to 3 times as high as that among persons who never smoked. Most of this excess mortality is believed to be explained by 21 common diseases that have been formally established as caused by cigarette smoking and are included in official estimates of smoking-attributable mortality in the United States. However, if smoking causes additional diseases, these official estimates may significantly underestimate the number of deaths attributable to smoking. METHODS: We pooled data from five contemporary U.S. cohort studies including 421,378 men and 532,651 women 55 years of age or older. Participants were followed from 2000 through 2011, and relative risks and 95% confidence intervals were estimated with the use of Cox proportional-hazards models adjusted for age, race, educational level, daily alcohol consumption, and cohort. RESULTS: During the follow-up period, there were 181,377 deaths, including 16,475 among current smokers. Overall, approximately 17% of the excess mortality among current smokers was due to associations with causes that are not currently established as attributable to smoking. These included associations between current smoking and deaths from renal failure (relative risk, 2.0; 95% confidence interval [CI], 1.7 to 2.3), intestinal ischemia (relative risk, 6.0; 95% CI, 4.5 to 8.1), hypertensive heart disease (relative risk, 2.4; 95% CI, 1.9 to 3.0), infections (relative risk, 2.3; 95% CI, 2.0 to 2.7), various respiratory diseases (relative risk, 2.0; 95% CI, 1.6 to 2.4), breast cancer (relative risk, 1.3; 95% CI, 1.2 to 1.5), and prostate cancer (relative risk, 1.4; 95% CI, 1.2 to 1.7). Among former smokers, the relative risk for each of these outcomes declined as the number of years since quitting increased. CONCLUSIONS: A substantial portion of the excess mortality among current smokers between 2000 and 2011 was due to associations with diseases that have not been formally established as caused by smoking. These associations should be investigated further and, when appropriate, taken into account when the mortality burden of smoking is investigated. (Funded by the American Cancer Society.).

Association of hand and arm disinfection with asthma control in US nurses.

OBJECTIVES: To investigate the association between occupational exposure to disinfectants/antiseptics used for hand hygiene and asthma control in nurses. METHODS: In 2014, we invited female nurses with asthma drawn from the Nurses' Health Study II to complete two supplemental questionnaires on their occupation and asthma (cross-sectional study, response rate: 80%). Among 4055 nurses (mean age: 59 years) with physician-diagnosed asthma and asthma medication use in the past year, we examined asthma control, as defined by the Asthma Control Test (ACT). Nurses were asked about the daily frequency of hand hygiene tasks: 'wash/scrub hands with disinfectants/hand sanitizers' (hand hygiene) and 'wash/scrub arms with disinfecting products' (surrogate of surgical hand/arm antisepsis). Analyses were adjusted for age, race, ethnicity, smoking status and body mass index. RESULTS: Nurses with partly controlled asthma (ACT: 20-24, 50%) and poorly controlled asthma (ACT ≤19, 18%) were compared with nurses with controlled asthma (ACT=25, 32%). In separate models, both hand and arm hygiene were associated with poorly controlled asthma. After mutual adjustment, only arm hygiene was associated with poorly controlled asthma: OR (95% CI) for <1 time/day, 1.38 (1.06 to 1.80); ≥1 time/day, 1.96 (1.52 to 2.51), versus never. We observed a consistent dose-response relationship between frequency of arm hygiene tasks (never to >10 times/day) and poor asthma control. Associations persisted after further adjustment for surfaces/instruments disinfection tasks. CONCLUSIONS: Frequency of hand/arm hygiene tasks in nurses was associated with poor asthma control. The results suggest an adverse effect of products used for surgical hand/arm antisepsis. This potential new occupational risk factor for asthma warrants further study.

Occupational exposure to disinfectants and asthma control in US nurses.

Disinfectant use has been associated with adverse respiratory effects among healthcare workers. However, the specific harmful agents have not been elucidated. We examined the association between occupational exposure to disinfectants and asthma control in the Nurses' Health Study II, a large cohort of female nurses.Nurses with asthma were invited in 2014 to complete two questionnaires on their current occupation and asthma (response rate 80%). Asthma control was defined by the Asthma Control Test (ACT). Exposure to major disinfectants was evaluated by a job-task-exposure matrix (JTEM).Analyses included 4102 nurses with asthma (mean age 58 years). Asthma control was poor (ACT score 16-19) in 12% of nurses and very poor (ACT score ≤15) in 6% of nurses. Use of disinfectants to clean medical instruments (19% exposed) was associated with poorly (OR 1.37; 95% CI 1.05-1.79) and very poorly (OR 1.88, 95% CI 1.38-2.56) controlled asthma (ptrend=0.004, after adjustment for potential confounders). Using JTEM estimates, exposure to formaldehyde, glutaraldehyde, hypochlorite bleach, hydrogen peroxide and enzymatic cleaners was associated with poor asthma control (all ptrend<0.05); exposure to quaternary ammonium compounds and alcohol was not.Use of several disinfectants was associated with poor asthma control. Our findings suggest targets for future efforts to prevent worsening of asthma control in healthcare workers.

Determinants of disinfectant use among nurses in U.S. healthcare facilities.

BACKGROUND: Disinfectant use among healthcare workers has been associated with respiratory disorders, especially asthma. We aimed to describe disinfectants used by U.S. nurses, and to investigate qualitative and quantitative differences according to workplace characteristics and region. METHODS: Disinfectant use was assessed by questionnaire in 8,851 nurses. Hospital characteristics were obtained from the American Hospital Association database. RESULTS: Working in a hospital was associated with higher disinfectant use (OR: 2.06 [95%CI: 1.89-2.24]), but lower spray use (0.74 [0.66-0.82]). Nurses working in smaller hospitals (<50 beds vs. ≥200 beds) were more likely to use disinfectants (1.69 [1.23-2.32]) and sprays (1.69 [1.20-2.38]). Spray use was lower in the West than in the Northeast (0.75 [0.58-0.97]). CONCLUSION: Disinfectant use was more common among nurses working in smaller hospitals, possibly because they perform more diverse tasks. Variations in spray use by hospital size and region suggest additional targets for future efforts to prevent occupational asthma. Am. J. Ind. Med. 60:131-140, 2017. © 2016 Wiley Periodicals, Inc.

Origin, Methods, and Evolution of the Three Nurses' Health Studies.

We have summarized the evolution of the Nurses' Health Study (NHS), a prospective cohort study of 121 700 married registered nurses launched in 1976; NHS II, which began in 1989 and enrolled 116 430 nurses; and NHS3, which began in 2010 and has ongoing enrollment. Over 40 years, these studies have generated long-term, multidimensional data, including lifestyle- and health-related information across the life course and an extensive repository of various biological specimens. We have described the questionnaire data collection, disease follow-up methods, biorepository resources, and data management and statistical procedures. Through integrative analyses, these studies have sustained a high level of scientific productivity and substantially influenced public health recommendations. We have highlighted recent interdisciplinary research projects and discussed future directions for collaboration and innovation.

Association Between Rotating Night Shift Work and Risk of Coronary Heart Disease Among Women.

IMPORTANCE: Prospective studies linking shift work to coronary heart disease (CHD) have been inconsistent and limited by short follow-up. OBJECTIVE: To determine whether rotating night shift work is associated with CHD risk. DESIGN, SETTING, AND PARTICIPANTS: Prospective cohort study of 189,158 initially healthy women followed up over 24 years in the Nurses' Health Studies (NHS [1988-2012]: N = 73,623 and NHS2 [1989-2013]: N = 115,535). EXPOSURES: Lifetime history of rotating night shift work (≥3 night shifts per month in addition to day and evening shifts) at baseline (updated every 2 to 4 years in the NHS2). MAIN OUTCOMES AND MEASURES: Incident CHD; ie, nonfatal myocardial infarction, CHD death, angiogram-confirmed angina pectoris, coronary artery bypass graft surgery, stents, and angioplasty. RESULTS: During follow-up, 7303 incident CHD cases occurred in the NHS (mean age at baseline, 54.5 years) and 3519 in the NHS2 (mean age, 34.8 years). In multivariable-adjusted Cox proportional hazards models, increasing years of baseline rotating night shift work was associated with significantly higher CHD risk in both cohorts. In the NHS, the association between duration of shift work and CHD was stronger in the first half of follow-up than in the second half (P=.02 for interaction), suggesting waning risk after cessation of shift work. Longer time since quitting shift work was associated with decreased CHD risk among ever shift workers in the NHS2 (P<.001 for trend). [table: see text] CONCLUSIONS AND RELEVANCE: Among women who worked as registered nurses, longer duration of rotating night shift work was associated with a statistically significant but small absolute increase in CHD risk. Further research is needed to explore whether the association is related to specific work hours and individual characteristics.

Asthma history, job type and job changes among US nurses.

OBJECTIVES: Nurses are at increased risk of occupational asthma, an observation that may be related to disinfectants exposure. Whether asthma history influences job type or job changes among nurses is unknown. We investigated this issue in a large cohort of nurses. METHODS: The Nurses' Health Study II is a prospective study of US female nurses enrolled in 1989 (ages 24-44 years). Job status and asthma were assessed in biennial (1989-2011) and asthma-specific questionnaires (1998, 2003). Associations between asthma history at baseline (diagnosis before 1989, n=5311) and job type at baseline were evaluated by multinomial logistic regression. The relations of asthma history and severity during follow-up to subsequent job changes were evaluated by Cox models. RESULTS: The analytic cohort included 98 048 nurses. Compared with nurses in education/administration (likely low disinfectant exposure jobs), women with asthma history at baseline were less often employed in jobs with likely high disinfectant exposure, such as operating rooms (odds ratio 0.73 (95% CI 0.63 to 0.86)) and emergency room/inpatient units (0.89 (0.82 to 0.97)). During a 22-year follow-up, nurses with a baseline history of asthma were more likely to move to jobs with lower exposure to disinfectants (HR 1.13 (1.07 to 1.18)), especially among those with more severe asthma (HR for mild persistent: 1.13; moderate persistent 1.26; severe persistent: 1.50, compared with intermittent asthma, p trend: 0.004). CONCLUSIONS: Asthma history was associated with baseline job type and subsequent job changes among nurses. This may partly reflect avoidance of tasks involving disinfectant use, and may introduce bias in cross-sectional studies on disinfectant exposure and asthma in nurses.

Healthful and Unhealthful Plant-Based Diets and Chronic Obstructive Pulmonary Disease in U.S. Adults: Prospective Study.

BACKGROUND: Despite the potential protective effect of a plant-based diet against chronic obstructive pulmonary disease (COPD), it remains unknown whether intake of different types of plant foods is beneficial for COPD. Our aims were to determine whether adherence to the healthful version of a plant-based diet (healthful Plant-based Diet Index (hPDI)) is associated with a lower COPD risk, whereas adherence to the unhealthful version (unhealthful Plant-based Diet Index (uPDI)) is associated with a higher COPD risk. METHODS: 46,948 men from the Health Professionals Follow-up Study, 73,592 women from the Nurses' Health Study, and 85,515 women from the Nurses' Health Study II who completed biennial questionnaires from 1984-2018. We derived diet scores from repeated validated food frequency questionnaires. Among 5,661,994 person-years of follow-up, we documented 2605 validated COPD cases between 1984-2018. RESULTS: After tight control for smoking and other potential confounders, COPD risk was 46% lower among participants with the highest hPDI score compared to those with the lowest score. Conversely, COPD risk was 39% higher among participants with the highest uPDI. Further adjustment for processed meat intake led to similar results. CONCLUSIONS: These findings provide further evidence for consuming a diet that emphasizes healthful plant foods to optimize lung health.

Tau Positron Emission Tomography and Neurocognitive Function Among Former Professional American-Style Football Players.

American-style football (ASF) players experience repetitive head impacts that may result in chronic traumatic encephalopathy neuropathological change (CTE-NC). At present, a definitive diagnosis of CTE-NC requires the identification of localized hyperphosphorylated Tau (p-Tau) after death via immunohistochemistry. Some studies suggest that positron emission tomography (PET) with the radiotracer [18F]-Flortaucipir (FTP) may be capable of detecting p-Tau and thus establishing a diagnosis of CTE-NC among living former ASF players. To assess associations between FTP, football exposure, and objective neuropsychological measures among former professional ASF players, we conducted a study that compared former professional ASF players with age-matched male control participants without repetitive head impact exposure. Former ASF players and male controls underwent structural magnetic resonance imaging and PET using FTP for p-Tau and [11C]-PiB for amyloid-ß. Former players underwent neuropsychological testing. The ASF exposure was quantified as age at first exposure, professional career duration, concussion signs and symptoms burden, and total years of any football play. Neuropsychological testing included measures of memory, executive functioning, and depression symptom severity. P-Tau was quantified as FTP standardized uptake value ratios (SUVR) and [11C]-PiB by distribution volume ratios (DVR) using cerebellar grey matter as the reference region. There were no significant differences in [18F]-FTP uptake among former ASF players (n = 27, age = 50 ± 7 years) compared with control participants (n = 11, age = 55 ± 4 years), nor did any participant have significant amyloid-ß burden. Among ASF participants, there were no associations between objective measures of neurocognitive functioning and [18F]-FTP uptake. There was a marginally significant difference, however, between [18F]-FTP uptake isolated to the entorhinal cortex among players in age-, position-, and race-adjusted models (p = 0.05) that may represent an area of future investigation. The absence of increased [18F]-FTP uptake in brain regions previously implicated in CTE among former professional ASF players compared with controls questions the utility of [18F]-FTP PET for clinical evaluation in this population.

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.

Association of Traumatic Brain Injury With the Risk of Developing Chronic Cardiovascular, Endocrine, Neurological, and Psychiatric Disorders.

Importance: Increased risk of neurological and psychiatric conditions after traumatic brain injury (TBI) is well-defined. However, cardiovascular and endocrine comorbidity risk after TBI in individuals without these comorbidities and associations with post-TBI mortality have received little attention. Objective: To assess the incidence of cardiovascular, endocrine, neurological, and psychiatric comorbidities in patients with mild TBI (mTBI) or moderate to severe TBI (msTBI) and analyze associations between post-TBI comorbidities and mortality. Design, Setting, and Participants: This prospective longitudinal cohort study used hospital-based patient registry data from a tertiary academic medical center to select patients without any prior clinical comorbidities who experienced TBI from 2000 to 2015. Using the same data registry, individuals without head injuries, the unexposed group, and without target comorbidities were selected and age-, sex-, and race-frequency-matched to TBI subgroups. Patients were followed-up for up to 10 years. Data were analyzed in 2021. Exposures: Mild or moderate to severe head trauma. Main Outcomes and Measures: Cardiovascular, endocrine, neurologic, and psychiatric conditions were defined based on International Classification of Diseases, Ninth Revision (ICD-9) or International Statistical Classification of Diseases and Related Health Problems, Tenth Revision (ICD-10). Associations between TBI and comorbidities, as well as associations between the comorbidities and mortality, were analyzed. Results: A total of 4351 patients with mTBI (median [IQR] age, 45 [29-57] years), 4351 patients with msTBI (median [IQR] age, 47 [30-58] years), and 4351 unexposed individuals (median [IQR] age, 46 [30-58] years) were included in analyses. In each group, 45% of participants were women. mTBI and msTBI were significantly associated with higher risks of cardiovascular, endocrine, neurologic, and psychiatric disorders compared with unexposed individuals. In particular, hypertension risk was increased in both mTBI (HR, 2.5; 95% CI, 2.1-2.9) and msTBI (HR, 2.4; 95% CI, 2.0-2.9) groups. Diabetes risk was increased in both mTBI (HR, 1.9; 95% CI, 1.4-2.7) and msTBI (HR, 1.9; 95% CI, 1.4-2.6) groups, and risk of ischemic stroke or transient ischemic attack was also increased in mTBI (HR, 2.2; 95% CI, 1.4-3.3) and msTBI (HR, 3.6; 95% CI, 2.4-5.3) groups. All comorbidities in the TBI subgroups emerged within a median (IQR) of 3.49 (1.76-5.96) years after injury. Risks for post-TBI comorbidities were also higher in patients aged 18 to 40 years compared with age-matched unexposed individuals: hypertension risk was increased in the mTBI (HR, 5.9; 95% CI, 3.9-9.1) and msTBI (HR, 3.9; 95% CI, 2.5-6.1) groups, while hyperlipidemia (HR, 2.3; 95% CI, 1.5-3.4) and diabetes (HR, 4.6; 95% CI, 2.1-9.9) were increased in the mTBI group. Individuals with msTBI, compared with unexposed patients, had higher risk of mortality (432 deaths [9.9%] vs 250 deaths [5.7%]; P < .001); postinjury hypertension (HR, 1.3; 95% CI, 1.1-1.7), coronary artery disease (HR, 2.2; 95% CI, 1.6-3.0), and adrenal insufficiency (HR, 6.2; 95% CI, 2.8-13.0) were also associated with higher mortality. Conclusions and Relevance: These findings suggest that TBI of any severity was associated with a higher risk of chronic cardiovascular, endocrine, and neurological comorbidities in patients without baseline diagnoses. Medical comorbidities were observed in relatively young patients with TBI. Comorbidities occurring after TBI were associated with higher mortality. These findings suggest the need for a targeted screening program for multisystem diseases after TBI, particularly chronic cardiometabolic diseases.

John Hutchinson, 1811-1861: the first respiratory disease epidemiologist.

In 1844, before a large medical audience in London, John Hutchinson demonstrated the use of measurements of pulmonary function to predict disease. In contrast to standard practice at that time, he conducted an epidemiological investigation that would have been acceptable by today's standards, in which he examined over 2000 people and contrasted healthy and diseased cases. His data clearly indicated how, what he called, "vital capacity" predicted disease. Exploring the history of this young Victorian-era physician is both humbling and instructive for the modern epidemiologist, who has the advantages of the successes of ever more rapid, computer-based, technical approaches to evaluate existing data sources, and fewer opportunities to actually collect primary data from large number of patients using physiologic tools.

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.

Pooled analyses of 13 prospective cohort studies on folate intake and colon cancer.

OBJECTIVE: Studies of folate intake and colorectal cancer risk have been inconsistent. We examined the relation with colon cancer risk in a series of 13 prospective studies. METHODS: Study- and sex-specific relative risks (RRs) were estimated from the primary data using Cox proportional hazards models and then pooled using a random-effects model. RESULTS: Among 725,134 participants, 5,720 incident colon cancers were diagnosed during follow-up. The pooled multivariate RRs (95% confidence interval [CI]) comparing the highest vs. lowest quintile of intake were 0.92 (95% CI 0.84-1.00, p-value, test for between-studies heterogeneity = 0.85) for dietary folate and 0.85 (95% CI 0.77-0.95, p-value, test for between-studies heterogeneity = 0.42) for total folate. Results for total folate intake were similar in analyses using absolute intake cutpoints (pooled multivariate RR = 0.87, 95% CI 0.78-0.98, comparing ≥ 560 mcg/days vs. <240 mcg/days, p-value, test for trend = 0.009). When analyzed as a continuous variable, a 2% risk reduction (95% CI 0-3%) was estimated for every 100 µg/day increase in total folate intake. CONCLUSION: These data support the hypothesis that higher folate intake is modestly associated with reduced risk of colon cancer.