IMPORTANCE: Players of American football may be at increased risk of long-term neurological conditions, particularly chronic traumatic encephalopathy (CTE). OBJECTIVE: To determine the ...neuropathological and clinical features of deceased football players with CTE. DESIGN, SETTING, AND PARTICIPANTS: Case series of 202 football players whose brains were donated for research. Neuropathological evaluations and retrospective telephone clinical assessments (including head trauma history) with informants were performed blinded. Online questionnaires ascertained athletic and military history. EXPOSURES: Participation in American football at any level of play. MAIN OUTCOMES AND MEASURES: Neuropathological diagnoses of neurodegenerative diseases, including CTE, based on defined diagnostic criteria; CTE neuropathological severity (stages I to IV or dichotomized into mild stages I and II and severe stages III and IV); informant-reported athletic history and, for players who died in 2014 or later, clinical presentation, including behavior, mood, and cognitive symptoms and dementia. RESULTS: Among 202 deceased former football players (median age at death, 66 years interquartile range, 47-76 years), CTE was neuropathologically diagnosed in 177 players (87%; median age at death, 67 years interquartile range, 52-77 years; mean years of football participation, 15.1 SD, 5.2), including 0 of 2 pre–high school, 3 of 14 high school (21%), 48 of 53 college (91%), 9 of 14 semiprofessional (64%), 7 of 8 Canadian Football League (88%), and 110 of 111 National Football League (99%) players. Neuropathological severity of CTE was distributed across the highest level of play, with all 3 former high school players having mild pathology and the majority of former college (27 56%), semiprofessional (5 56%), and professional (101 86%) players having severe pathology. Among 27 participants with mild CTE pathology, 26 (96%) had behavioral or mood symptoms or both, 23 (85%) had cognitive symptoms, and 9 (33%) had signs of dementia. Among 84 participants with severe CTE pathology, 75 (89%) had behavioral or mood symptoms or both, 80 (95%) had cognitive symptoms, and 71 (85%) had signs of dementia. CONCLUSIONS AND RELEVANCE: In a convenience sample of deceased football players who donated their brains for research, a high proportion had neuropathological evidence of CTE, suggesting that CTE may be related to prior participation in football.
Objective
The prevalence of symptomatic knee osteoarthritis (OA) has been increasing over the past several decades in the US, concurrent with an aging population and the growing obesity epidemic. We ...quantify the impact of these factors on the number of persons with symptomatic knee OA in the early decades of the 21st century.
Methods
We calculated the prevalence of clinically diagnosed symptomatic knee OA from the National Health Interview Survey 2007–2008 and derived the proportion with advanced disease (defined as Kellgren/Lawrence grade 3 or 4) using the Osteoarthritis Policy Model, a validated simulation model of knee OA. Incorporating contemporary obesity rates and population estimates, we calculated the number of persons living with symptomatic knee OA.
Results
We estimate that approximately 14 million persons had symptomatic knee OA, with advanced OA comprising more than half of those cases. This includes more than 3 million persons of racial/ethnic minorities (African American, Hispanic, and other). Adults younger than 45 years of age represented nearly 2 million cases of symptomatic knee OA and individuals between 45 and 65 years of age comprised 6 million more cases.
Conclusion
More than half of all persons with symptomatic knee OA are younger than 65 years of age. As many of these younger persons will live for 3 decades or more, there is substantially more time for greater disability to occur, and policymakers should anticipate health care utilization for knee OA to increase in the upcoming decades. These data emphasize the need for the deployment of innovative prevention and treatment strategies for knee OA, especially among younger persons.
Heart failure with preserved ejection fraction (HFpEF) is a heterogeneous clinical syndrome in need of improved phenotypic classification. We sought to evaluate whether unbiased clustering analysis ...using dense phenotypic data (phenomapping) could identify phenotypically distinct HFpEF categories.
We prospectively studied 397 patients with HFpEF and performed detailed clinical, laboratory, ECG, and echocardiographic phenotyping of the study participants. We used several statistical learning algorithms, including unbiased hierarchical cluster analysis of phenotypic data (67 continuous variables) and penalized model-based clustering, to define and characterize mutually exclusive groups making up a novel classification of HFpEF. All phenomapping analyses were performed by investigators blinded to clinical outcomes, and Cox regression was used to demonstrate the clinical validity of phenomapping. The mean age was 65±12 years; 62% were female; 39% were black; and comorbidities were common. Although all patients met published criteria for the diagnosis of HFpEF, phenomapping analysis classified study participants into 3 distinct groups that differed markedly in clinical characteristics, cardiac structure/function, invasive hemodynamics, and outcomes (eg, phenogroup 3 had an increased risk of HF hospitalization hazard ratio, 4.2; 95% confidence interval, 2.0-9.1 even after adjustment for traditional risk factors P<0.001). The HFpEF phenogroup classification, including its ability to stratify risk, was successfully replicated in a prospective validation cohort (n=107).
Phenomapping results in a novel classification of HFpEF. Statistical learning algorithms applied to dense phenotypic data may allow improved classification of heterogeneous clinical syndromes, with the ultimate goal of defining therapeutically homogeneous patient subclasses.
Health care utilization databases have been increasingly used for studies of rheumatoid arthritis (RA). However, the accuracy of RA diagnoses in these data has been inconsistent.
Using medical ...records and a standardized abstraction form, we examined the positive predictive value (PPV) of several algorithms to define RA diagnosis using claims data: A) at least two visits coded for RA (ICD-9, 714); B) at least three visits coded for RA; and C) at least two visits to a rheumatologist for RA. We also calculated the PPVs for the subgroups identified by these algorithms combined with pharmacy claims data for at least one disease-modifying anti-rheumatic drug (DMARD) prescription.
We invited 9,482 Medicare beneficiaries with pharmacy benefits in Pennsylvania to participate; 2% responded and consented for review of their medical records. There was no difference in characteristics between respondents and non-respondents. Using 'RA diagnosis per rheumatologists' as the gold standard, the PPVs were 55.7% for at least two claims coded for RA, 65.5% for at least three claims for RA, and 66.7% for at least two rheumatology claims for RA. The PPVs of these algorithms in patients with at least one DMARD prescription increased to 86.2%-88.9%. When fulfillment of 4 or more of the ACR RA criteria was used as the gold standard, the PPVs of the algorithms combined with at least one DMARD prescriptions were 55.6%-60.7%.
To accurately identify RA patients in health care utilization databases, algorithms that include both diagnosis codes and DMARD prescriptions are recommended.
Objective
To examine the effect of age of first exposure to tackle football on chronic traumatic encephalopathy (CTE) pathological severity and age of neurobehavioral symptom onset in tackle football ...players with neuropathologically confirmed CTE.
Methods
The sample included 246 tackle football players who donated their brains for neuropathological examination. Two hundred eleven were diagnosed with CTE (126 of 211 were without comorbid neurodegenerative diseases), and 35 were without CTE. Informant interviews ascertained age of first exposure and age of cognitive and behavioral/mood symptom onset.
Results
Analyses accounted for decade and duration of play. Age of exposure was not associated with CTE pathological severity, or Alzheimer's disease or Lewy body pathology. In the 211 participants with CTE, every 1 year younger participants began to play tackle football predicted earlier reported cognitive symptom onset by 2.44 years (p < 0.0001) and behavioral/mood symptoms by 2.50 years (p < 0.0001). Age of exposure before 12 predicted earlier cognitive (p < 0.0001) and behavioral/mood (p < 0.0001) symptom onset by 13.39 and 13.28 years, respectively. In participants with dementia, younger age of exposure corresponded to earlier functional impairment onset. Similar effects were observed in the 126 CTE‐only participants. Effect sizes were comparable in participants without CTE.
Interpretation
In this sample of deceased tackle football players, younger age of exposure to tackle football was not associated with CTE pathological severity, but predicted earlier neurobehavioral symptom onset. Youth exposure to tackle football may reduce resiliency to late‐life neuropathology. These findings may not generalize to the broader tackle football population, and informant‐report may have affected the accuracy of the estimated effects. Ann Neurol 2018;83:886–901
Objective
To estimate the incidence and lifetime risk of diagnosed symptomatic knee osteoarthritis (OA) and the age at diagnosis of knee OA based on self‐reports in the US population.
Methods
We ...estimated the incidence of diagnosed symptomatic knee OA in the US by combining data on age‐, sex‐, and obesity‐specific prevalence from the 2007–2008 National Health Interview Survey, with disease duration estimates derived from the Osteoarthritis Policy (OAPol) Model, a validated computer simulation model of knee OA. We used the OAPol Model to estimate the mean and median ages at diagnosis and lifetime risk.
Results
The estimated incidence of diagnosed symptomatic knee OA was highest among adults ages 55–64 years, ranging from 0.37% per year for nonobese men to 1.02% per year for obese women. The estimated median age at knee OA diagnosis was 55 years. The estimated lifetime risk was 13.83%, ranging from 9.60% for nonobese men to 23.87% in obese women. Approximately 9.29% of the US population is diagnosed with symptomatic knee OA by age 60 years.
Conclusion
The diagnosis of symptomatic knee OA occurs relatively early in life, suggesting that prevention programs should be offered relatively early in the life course. Further research is needed to understand the future burden of health care utilization resulting from earlier diagnosis of knee OA.
The long-term consequences of repetitive head impacts have been described since the early 20th century. Terms such as punch drunk and dementia pugilistica were first used to describe the clinical ...syndromes experienced by boxers. A more generic designation, chronic traumatic encephalopathy (CTE), has been employed since the mid-1900s and has been used in recent years to describe a neurodegenerative disease found not just in boxers but in American football players, other contact sport athletes, military veterans, and others with histories of repetitive brain trauma, including concussions and subconcussive trauma. This article reviews the literature of the clinical manifestations of CTE from 202 published cases. The clinical features include impairments in mood (for example, depression and hopelessness), behavior (for example, explosivity and violence), cognition (for example, impaired memory, executive functioning, attention, and dementia), and, less commonly, motor functioning (for example, parkinsonism, ataxia, and dysarthria). We present proposed research criteria for traumatic encephalopathy syndrome (TES) which consist of four variants or subtypes (TES behavioral/mood variant, TES cognitive variant, TES mixed variant, and TES dementia) as well as classifications of 'probable CTE' and 'possible CTE'. These proposed criteria are expected to be modified and updated as new research findings become available. They are not meant to be used for a clinical diagnosis. Rather, they should be viewed as research criteria that can be employed in studies of the underlying causes, risk factors, differential diagnosis, prevention, and treatment of CTE and related disorders.
Objective
Chronic traumatic encephalopathy (CTE) is a neurodegenerative disease associated with exposure to contact and collision sports, including American football. We hypothesized a dose–response ...relationship between duration of football played and CTE risk and severity.
Methods
In a convenience sample of 266 deceased American football players from the Veterans Affairs–Boston University–Concussion Legacy Foundation and Framingham Heart Study Brain Banks, we estimated the association of years of football played with CTE pathological status and severity. We evaluated the ability of years played to classify CTE status using receiver operating characteristic curve analysis. Simulation analyses quantified conditions that might lead to selection bias.
Results
In total, 223 of 266 participants met neuropathological diagnostic criteria for CTE. More years of football played were associated with having CTE (odds ratio OR = 1.30 per year played, 95% confidence interval CI = 1.19–1.41; p = 3.8 × 10−9) and with CTE severity (severe vs mild; OR = 1.14 per year played, 95% CI = 1.07–1.22; p = 3.1 × 10−4). Participants with CTE were 1/10th as likely to have played <4.5 years (negative likelihood ratio LR = 0.102, 95% CI = 0.100–0.105) and were 10 times as likely to have played >14.5 years (positive LR = 10.2, 95% CI = 9.8–10.7) compared with participants without CTE. Sensitivity and specificity were maximized at 11 years played. Simulation demonstrated that years played remained adversely associated with CTE status when years played and CTE status were both related to brain bank selection across widely ranging scenarios.
Interpretation
The odds of CTE double every 2.6 years of football played. After accounting for brain bank selection, the magnitude of the relationship between years played and CTE status remained consistent. ANN NEUROL 2020;87:116–131
Objective
Osteoarthritis (OA) of the knee is a painful condition affecting ∼13% of persons ages >65 years. We sought to examine whether the use of opioids in older persons with OA has increased over ...the past decade and what patient characteristics may correlate with their use.
Methods
We assembled national cohorts of individuals with knee OA using data from the 2003, 2006, and 2009 waves of the Medicare Current Beneficiary Survey. The survey data contained information on demographics, health status, and prescribed medications linked to Medicare claims. We used multivariate logistic regression to establish whether opioid use changed over time and to identify factors associated with greater opioid use. The outcome was defined as receiving ≥1 opioid prescription in the study year.
Results
The mean age and sex were similar across years (77 years and 69% women, respectively). There was a significant increase in opioid prescribing between 2003 and 2009, with 31% of patients receiving opioids in 2003, 39% in 2006, and 40% in 2009 (odds ratio OR 1.5, 95% confidence interval 95% CI 1.1–2.0 for 2006 and 2009 compared with 2003). Independent correlates of opioid use across time periods included female sex (OR 1.5, 95% CI 1.2–2.0), functional limitation (OR 2.1, 95% CI 1.6–2.7), poor self‐reported health status (OR 1.6, 95% CI 1.2–2.0), chronic obstructive pulmonary disease (OR 1.4, 95% CI 1.0–1.8), and musculoskeletal disease besides OA (OR 1.9, 95% CI 1.2–2.8).
Conclusion
As the prevalence and incidence of knee OA continues to increase, the public health impact of greater opioid use should be monitored carefully.
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