Michael D. McClean

Clinicopathological evaluation of chronic traumatic encephalopathy in players of American football

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.

Age of first exposure to American football and long-term neuropsychiatric and cognitive outcomes

Previous research suggests that age of first exposure (AFE) to football before age 12 may have long-term clinical implications; however, this relationship has only been examined in small samples of former professional football players. We examined the association between AFE to football and behavior, mood and cognition in a large cohort of former amateur and professional football players. The sample included 214 former football players without other contact sport history. Participants completed the Brief Test of Adult Cognition by Telephone (BTACT), and self-reported measures of executive function and behavioral regulation (Behavior Rating Inventory of Executive Function-Adult Version Metacognition Index (MI), Behavioral Regulation Index (BRI)), depression (Center for Epidemiologic Studies Depression Scale (CES-D)) and apathy (Apathy Evaluation Scale (AES)). Outcomes were continuous and dichotomized as clinically impaired. AFE was dichotomized into <12 and ⩾12, and examined continuously. Multivariate mixed-effect regressions controlling for age, education and duration of play showed AFE to football before age 12 corresponded with >2 × increased odds for clinically impaired scores on all measures but BTACT: (odds ratio (OR), 95% confidence interval (CI): BRI, 2.16,1.19–3.91; MI, 2.10,1.17–3.76; CES-D, 3.08,1.65–5.76; AES, 2.39,1.32–4.32). Younger AFE predicted increased odds for clinical impairment on the AES (OR, 95% CI: 0.86, 0.76–0.97) and CES-D (OR, 95% CI: 0.85, 0.74–0.97). There was no interaction between AFE and highest level of play. Younger AFE to football, before age 12 in particular, was associated with increased odds for impairment in self-reported neuropsychiatric and executive function in 214 former American football players. Longitudinal studies will inform youth football policy and safety decisions.

White matter signal abnormalities in former National Football League players

Later‐life brain alterations in former tackle football players are poorly understood, particularly regarding their relationship with repetitive head impacts (RHIs) and clinical function. We examined white matter signal abnormalities (WMSAs) and their association with RHIs and clinical function in former National Football League (NFL) players.

Leptospira seropositivity as a risk factor for Mesoamerican Nephropathy

Abstract Background: Leptospirosis is postulated as a possible cause of Mesoamerican Nephropathy (MeN) in Central American workers. Objectives: Investigate job-specific Leptospira seroprevalence and its association with kidney disease biomarkers. Methods: In 282 sugarcane workers, 47 sugarcane applicants and 160 workers in other industries, we measured anti-leptospiral antibodies, serum creatinine, and urinary injury biomarkers, including neutrophil gelatinase-associated lipocalin (NGAL), interleukin-18 (IL-18), and N-acetyl-D-glucosaminidase (NAG). Results: Leptospira seroprevalence differed among job categories and was highest among sugarcane cutters (59%). Seropositive sugarcane workers had higher NGAL concentrations (relative mean: 1.28; 95% CI: 0.94–1.75) compared to those who were seronegative, with similar findings among field and non-field workers. Conclusions: Leptospira seroprevalence varied by job category. There was some indication that seropositivity was associated with elevated biomarker levels, but results were inconsistent. Additional studies may help establish whether Leptospira infection plays any role in MeN among Central American workers.

Acute Kidney Injury in Sugarcane Workers at Risk for Mesoamerican Nephropathy

RATIONALE & OBJECTIVEnMesoamerican nephropathy (MeN), a form of chronic kidney disease (CKD) of unknown cause in Central America, affects young individuals working in physically strenuous occupations. Repeated episodes of work-related kidney injury may lead to CKD in this setting. We aimed to better understand the burden and natural history of acute kidney injury (AKI) in workers at risk for MeN.nnnSTUDY DESIGNnCross-sectional study of active sugarcane workers, followed by prospective follow-up of individuals with AKI.nnnSETTING & PARTICIPANTSn326 sugarcane workers with normal preharvest serum creatinine (Scr) values and no history of CKD in an MeN hotspot in Nicaragua near the end of the harvest, and prospective follow-up of workers with AKI.nnnPREDICTORnAKI during the harvest, as defined by Scr level increasexa0≥ 0.3mg/dL over baseline to a levelxa0≥ 1.3mg/dL.nnnOUTCOMESnKidney function trajectory and development of CKD over 12 months.nnnANALYTICAL APPROACHnLinear regression models were used to analyze the association between job category and kidney function. For workers with AKI, the effect of time on Scr level was evaluated using linear mixed effects.nnnRESULTSn34 of 326 participants were found to have AKI, with a median late-harvest Scr level of 1.64mg/dL in the AKI group. Workers without AKI had a median Scr level of 0.88mg/dL. AKI was more common among cane cutters compared with other field workers. Participants with AKI had variable degrees of kidney function recovery, with median 6- and 12-month Scr values of 1.25 and 1.27mg/dL, respectively (Pxa0< 0.001 for each follow-up value compared to late-harvest Scr). When we compared workers kidney function before the AKI episode to their kidney function at last follow-up, 10 participants with AKI developed de novo estimated glomerular filtration ratexa0< 60mL/min/1.73m2 and 11 had a >30% decrease in estimated glomerular filtration rate.nnnLIMITATIONSnFollow-up limited to 1 year and some loss to follow-up in the prospective component of the study. Broad definition of AKI that includes both acute and subacute kidney injury.nnnCONCLUSIONSnIn a group of sugarcane workers with normal preharvest kidney function, newly decreased kidney function developing during the harvest season was common. Of those with kidneyxa0injury, nearly half had established CKD 12 months later.

Meta-analysis of self-reported health symptoms in 1990–1991 Gulf War and Gulf War-era veterans

Objectives Across diverse groups of Gulf War (GW) veterans, reports of musculoskeletal pain, cognitive dysfunction, unexplained fatigue, chronic diarrhoea, rashes and respiratory problems are common. GW illness is a condition resulting from GW service in veterans who report a combination of these symptoms. This study integrated the GW literature using meta-analytical methods to characterise the most frequently reported symptoms occurring among veterans who deployed to the 1990–1991 GW and to better understand the magnitude of ill health among GW-deployed veterans compared with non-deployed GW-era veterans. Design Meta-analysis. Methods Literature databases were searched for peer-reviewed studies published from January 1990 to May 2017 reporting health symptom frequencies in GW-deployed veterans and GW-era control veterans. Self-reported health symptom data were extracted from 21 published studies. A binomial-normal meta-analytical model was used to determine pooled prevalence of individual symptoms in GW-deployed veterans and GW-era control veterans and to calculate combined ORs of health symptoms comparing GW-deployed veterans and GW-era control veterans. Results GW-deployed veterans had higher odds of reporting all 56 analysed symptoms compared with GW-era controls. Odds of reporting irritability (OR 3.21, 95%u2009CI 2.28 to 4.52), feeling detached (OR 3.59, 95%u2009CI 1.83 to 7.03), muscle weakness (OR 3.19, 95%u2009CI 2.73 to 3.74), diarrhoea (OR 3.24, 95%u2009CI 2.51 to 4.17) and rash (OR 3.18, 95%u2009CI 2.47 to 4.09) were more than three times higher among GW-deployed veterans compared with GW-era controls. Conclusions The higher odds of reporting mood-cognition, fatigue, musculoskeletal, gastrointestinal and dermatological symptoms among GW-deployed veterans compared with GW-era controls indicates these symptoms are important when assessing GW veteran health status.

Racial differences in the relationship between tobacco, alcohol, and the risk of head and neck cancer: pooled analysis of US studies in the INHANCE Consortium

There have been few published studies on differences between Blacks and Whites in the estimated effects of alcohol and tobacco use on the incidence of head and neck cancer (HNC) in the United States. Previous studies have been limited by small numbers of Blacks. Using pooled data from 13 US case–control studies of oral, pharyngeal, and laryngeal cancers in the International Head and Neck Cancer Epidemiology Consortium, this study comprised a large number of Black HNC cases (nu2009=u2009975). Logistic regression was used to estimate adjusted odds ratios (OR) and 95% confidence intervals (CI) for several tobacco and alcohol consumption characteristics. Blacks were found to have consistently stronger associations than Whites for the majority of tobacco consumption variables. For example, compared to never smokers, Blacks who smoked cigarettes for >u200930xa0years had an OR 4.53 (95% CI 3.22–6.39), which was larger than that observed in Whites (OR 3.01, 95% CI 2.73–3.33; pinteractionu2009<u20090.0001). The ORs for alcohol use were also larger among Blacks compared to Whites. Exclusion of oropharyngeal cases attenuated the racial differences in tobacco use associations but not alcohol use associations. These findings suggest modest racial differences exist in the association of HNC risk with tobacco and alcohol consumption.

JP8 exposure and neurocognitive performance among US Air Force personnel

HIGHLIGHTSRepeated acute exposure to JP8 over a work week was not significantly related to reduced neurocognitive proficiencies.JP8 exposure was measured at levels below regulated occupational exposure guidelines.More years of Air Force service was not significantly associated with diminished neurocognitive performances. ABSTRACT Petroleum‐based fuels such as jet propellant (JP) 4, JP5, JP8, and jet A1 (JetA) are among the most common occupational chemical exposures encountered by military and civilian workforces. Although acute toxicity following high‐level exposures to JP8 and similar chemical mixtures has been reported, the relationship between persistent low‐level occupational exposures to jet fuels and both acute and longer‐term central nervous system (CNS) function has been comparatively less well characterized. This paper describes results of neurocognitive assessments acquired repeatedly across a work week study design (Friday to Friday) as part of the Occupational JP8 Exposure Neuroepidemiology Study (OJENES) involving U.S. Air Force (AF) personnel with varying levels of exposure to jet fuel (JP8). JP8 exposure levels were quantified using both personal air monitoring and urinary biomarkers of exposure. Neurocognitive performance was evaluated using an objective, standardized battery of tests. No significant associations with neurocognitive performances were observed between individuals having regular contact and those with minimal/no direct contact with JP8 (measured by average work week levels of personal breathing zone exposure). Also, no significant findings were noted between repeated measures of absorbed dose (multi‐day pre‐shift urinary 1‐ and 2‐naphthol) and reduced proficiency on neurocognitive tasks across the work week. Results suggest that occupational exposure to lower (than regulated standards) levels of JP8 do not appear to be associated with acute, measurable differences or changes in neurocognitive performance.

Dietary fiber intake and head and neck cancer risk: A pooled analysis in the International Head and Neck Cancer Epidemiology consortium

The possible role of dietary fiber in the etiology of head neck cancers (HNCs) is unclear. We used individual‐level pooled data from ten case‐control studies (5959 cases and 12,248 controls) participating in the International Head and Neck Cancer Epidemiology (INHANCE) consortium, to examine the association between fiber intake and cancer of the oral cavity/pharynx and larynx. Odds Ratios (ORs) and their 95% Confidence Intervals (CIs) were estimated using unconditional multiple logistic regression applied to quintile categories of non‐alcohol energy‐adjusted fiber intake and adjusted for tobacco and alcohol use and other known or putative confounders. Fiber intake was inversely associated with oral and pharyngeal cancer combined (OR for 5th vs. 1st quintile categoryu2009=u20090.49, 95% CI: 0.40–0.59; p for trend <0.001) and with laryngeal cancer (ORu2009=u20090.66, 95% CI: 0.54–0.82, p for trend <0.001). There was, however, appreciable heterogeneity of the estimated effect across studies for oral and pharyngeal cancer combined. Nonetheless, inverse associations were consistently observed for the subsites of oral and pharyngeal cancers and within most strata of the considered covariates, for both cancer sites. Our findings from a multicenter large‐scale pooled analysis suggest that, although in the presence of between‐study heterogeneity, a greater intake of fiber may lower HNC risk.