Football’s InfluencE on Lifelong health and Dementia risk (FIELD): protocol for a retrospective cohort study of former professional footballers

Introduction: In the past decade, evidence has emerged suggesting a potential link between contact sport participation and increased risk of late neurodegenerative disease, in particular chronic traumatic encephalopathy. While there remains a lack of clear evidence to test the hypothesis that contact sport participation is linked to an increased incidence of dementia, there is growing public concern regarding the risk. There is, therefore, a pressing need for research to gain greater understanding of the potential risks involved in contact sports participation, and to contextualise these within holistic health benefits of sport. Methods and analysis: Football’s InfluencE on Lifelong health and Dementia risk is designed as a retrospective cohort study, with the aim to analyse data from former professional footballers (FPF) in order to assess the incidence of neurodegenerative disease in this population. Comprehensive electronic medical and death records will be analysed and compared with those of a demographically matched population control cohort. As well as neurodegenerative disease incidence, all-cause, and disease-specific mortality, will be analysed in order to assess lifelong health. Cox proportional hazards models will be run to compare the data collected from FPFs to matched population controls. Ethics and dissemination: Approvals for study have been obtained from the University of Glasgow College of Medical, Veterinary and Life Sciences Research Ethics Committee (Project Number 200160147) and from National Health Service Scotland’s Public Benefits and Privacy Panel (Application 1718-0120)

Neurodegenerative disease mortality among former professional soccer players

Background: Neurodegenerative disorders have been reported in elite athletes who participated in contact sports. The incidence of neurodegenerative disease among former professional soccer players has not been well characterized. Methods: We conducted a retrospective cohort study to compare mortality from neurodegenerative disease among 7676 former professional soccer players (identified from databases of Scottish players) with that among 23,028 controls from the general population who were matched to the players on the basis of sex, age, and degree of social deprivation. Causes of death were determined from death certificates. Data on medications dispensed for the treatment of dementia in the two cohorts were also compared. Prescription information was obtained from the national Prescribing Information System. Results: Over a median of 18 years, 1180 former soccer players (15.4%) and 3807 controls (16.5%) died. All-cause mortality was lower among former players than among controls up to the age of 70 years and was higher thereafter. Mortality from ischemic heart disease was lower among former players than among controls (hazard ratio, 0.80; 95% confidence interval [CI], 0.66 to 0.97; P=0.02), as was mortality from lung cancer (hazard ratio, 0.53; 95% CI, 0.40 to 0.70; P<0.001). Mortality with neurodegenerative disease listed as the primary cause was 1.7% among former soccer players and 0.5% among controls (subhazard ratio [the hazard ratio adjusted for competing risks of death from ischemic heart disease and death from any cancer], 3.45; 95% CI, 2.11 to 5.62; P<0.001). Among former players, mortality with neurodegenerative disease listed as the primary or a contributory cause on the death certificate varied according to disease subtype and was highest among those with Alzheimer’s disease (hazard ratio [former players vs. controls], 5.07; 95% CI, 2.92 to 8.82; P<0.001) and lowest among those with Parkinson’s disease (hazard ratio, 2.15; 95% CI, 1.17 to 3.96; P=0.01). Dementia-related medications were prescribed more frequently to former players than to controls (odds ratio, 4.90; 95% CI, 3.81 to 6.31; P<0.001). Mortality with neurodegenerative disease listed as the primary or a contributory cause did not differ significantly between goalkeepers and outfield players (hazard ratio, 0.73; 95% CI, 0.43 to 1.24; P=0.24), but dementia-related medications were prescribed less frequently to goalkeepers (odds ratio, 0.41; 95% CI, 0.19 to 0.89; P=0.02). Conclusions: In this retrospective epidemiologic analysis, mortality from neurodegenerative disease was higher and mortality from other common diseases lower among former Scottish professional soccer players than among matched controls. Dementia-related medications were prescribed more frequently to former players than to controls. These observations need to be confirmed in prospective matched-cohort studies. (Funded by the Football Association and Professional Footballers’ Association.

A cost effectiveness study of integrated care in health services delivery: a diabetes program in Australia

BACKGROUND: Type 2 diabetes is rapidly growing as a proportion of the disease burden in Australia as elsewhere. This study addresses the cost effectiveness of an integrated approach to assisting general practitioners (GPs) with diabetes management. This approach uses a centralized database of clinical data of an Australian Division of General Practice (a network of GPs) to co-ordinate care according to national guidelines. METHODS: Long term outcomes for patients in the program were derived using clinical parameters after 5 years of program participation, and the United Kingdom Prospective Diabetes Study (UKPDS) Outcomes Model, to project outcomes for 40 years from the time of diagnosis and from 5 years postdiagnosis. Cost information was obtained from a range of sources. While program costs are directly available, and costs of complications can be estimated from the UKPDS model, other costs are estimated by comparing costs in the Division with average costs across the state or the nation. The outcome and cost measures are used derive incremental cost-effectiveness ratios. RESULTS: The clinical data show that the program is effective in the short term, with improvement or no statistical difference in most clinical measures over 5 years. Average HbA1c levels increased by less than expected over the 5 year period. While the program is estimated to generate treatment cost savings, overall net costs are positive. However, the program led to projected improvements in expected life years and Quality Adjusted Life Expectancy (QALE), with incremental cost effectiveness ratios of $A8,106 per life-year saved and$A9,730 per year of QALE gained. CONCLUSIONS: The combination of an established model of diabetes progression and generally available data has provided an opportunity to establish robust methods of testing the cost effectiveness of a program for which a formal control group was not available. Based on this methodology, integrated health care delivery provided by a network of GPs improved health outcomes of type 2 diabetics with acceptable cost effectiveness, which suggests that similar outcomes may be obtained elsewhere

Association of field position and career length with risk of neurodegenerative disease in male former professional soccer players

Importance: Neurodegenerative disease mortality is higher among former professional soccer players than general population controls. However, the factors contributing to increased neurodegenerative disease mortality in this population remain uncertain. Objective: To investigate the association of field position, professional career length, and playing era with risk of neurodegenerative disease among male former professional soccer players. Design, Setting, and Participants: This cohort study used population-based health record linkage in Scotland to evaluate risk among 7676 male former professional soccer players born between January 1, 1900, and January 1, 1977, and 23 028 general population control individuals matched by year of birth, sex, and area socioeconomic status providing 1 812 722 person-years of follow-up. Scottish Morbidity Record and death certification data were available from January 1, 1981, to December 31, 2016, and prescribing data were available from January 1, 2009, to December 31, 2016. Database interrogation was performed on December 10, 2018, and data were analyzed between April 2020 and May 2021. Exposures: Participation in men’s soccer at a professional level. Main Outcomes and Measures: Outcomes were obtained by individual-level record linkage to national electronic records of mental health and general hospital inpatient and day-case admissions as well as prescribing information and death certification. Risk of neurodegenerative disease was evaluated between former professional soccer players and matched general population control individuals. Results: In this cohort study of 30 704 male individuals, 386 of 7676 former soccer players (5.0%) and 366 of 23 028 matched population control individuals (1.6%) were identified with a neurodegenerative disease diagnosis (hazard ratio [HR], 3.66; 95% CI, 2.88-4.65; P < .001). Compared with the risk among general population control individuals, risk of neurodegenerative disease was highest for defenders (HR, 4.98; 95% CI, 3.18-7.79; P < .001) and lowest for goalkeepers (HR, 1.83; 95% CI, 0.93-3.60; P = .08). Regarding career length, risk was highest among former soccer players with professional career lengths longer than 15 years (HR, 5.20; 95% CI, 3.17-8.51; P < .001). Regarding playing era, risk remained similar for all players born between 1910 and 1969. Conclusions and Relevance: The differences in risk of neurodegenerative disease observed in this cohort study imply increased risk with exposure to factors more often associated with nongoalkeeper positions, with no evidence this association has changed over the era studied. While investigations to confirm specific factors contributing to increased risk of neurodegenerative disease among professional soccer players are required, strategies directed toward reducing head impact exposure may be advisable in the meantime

Development of the ways of helping questionnaire: A measure of preferred coping strategies for older African American cancer survivors

Although researchers have identified beneficial coping strategies for cancer patients, existing coping measures do not capture the preferred coping strategies of older African American cancer survivors. A new measure, the Ways of Helping Questionnaire (WHQ), was evaluated with 385 African American cancer survivors. Validity evidence from factor analysis resulted in 10 WHQ subscales (Others There for Me, Physical and Treatment Care Needs, Help from God, Church Family Support, Helping Others, Being Strong for Others, Encouraging My Healthy Behaviors, Others Distract Me, Learning about Cancer, and Distracting Myself). Reliability evidence was generally strong. Evidence regarding hypothesized relationships with measures of well-being and another coping measure was mixed. The WHQ’s content coverage makes it especially relevant for older African American cancer survivors

Structural Impact of the Leukemia Drug 1-β-d-Arabinofuranosylcytosine (Ara-C) on the Covalent Human Topoisomerase I-DNA Complex

1-beta-d-Arabinofuranosylcytosine (Ara-C) is a potent antineoplastic drug used in the treatment of acute leukemia. Previous biochemical studies indicated the incorporation of Ara-C into DNA reduced the catalytic activity of human topoisomerase I by decreasing the rate of single DNA strand religation by the enzyme by 2-3-fold. We present the 3.1 A crystal structure of human topoisomerase I in covalent complex with an oligonucleotide containing Ara-C at the +1 position of the non-scissile DNA strand. The structure reveals that a hydrogen bond formed between the 2'-hydroxyl of Ara-C and the O4' of the adjacent -1 base 5' to the damage site stabilizes a C3'-endo pucker in the Ara-C arabinose ring. The structural distortions at the site of damage are translated across the DNA double helix to the active site of human topoisomerase I. The free sulfhydryl at the 5'-end of the nicked DNA strand in this trapped covalent complex is shifted out of alignment with the 3'-phosphotyrosine linkage at the catalytic tyrosine 723 residue, producing a geometry not optimal for religation. The subtle structural changes caused by the presence of Ara-C in the DNA duplex may contribute to the cytotoxicity of this leukemia drug by prolonging the lifetime of the covalent human topoisomerase I-DNA complex

Source tracking swine fecal waste in surface water proximal to swine concentrated animal feeding operations

Swine farming has gone through many changes in the last few decades, resulting in operations with a high animal density known as confined animal feeding operations (CAFOs). These operations produce a large quantity of fecal waste whose environmental impacts are not well understood. The purpose of this study was to investigate microbial water quality in surface waters proximal to swine CAFOs including microbial source tracking of fecal microbes specific to swine. For one year, surface water samples at up- and downstream sites proximal to swine CAFO lagoon waste land application sites were tested for fecal indicator bacteria (fecal coliforms, Escherichia coli and Enterococcus) and candidate swine-specific microbial source-tracking (MST) markers (Bacteroidales Pig-1-Bac, Pig-2-Bac, and Pig-Bac-2, and methanogen P23-2). Testing of 187 samples showed high fecal indicator bacteria concentrations at both up- and downstream sites. Overall, 40%, 23%, and 61% of samples exceeded state and federal recreational water quality guidelines for fecal coliforms, E. coli, and Enterococcus, respectively. Pig-1-Bac and Pig-2-Bac showed the highest specificity to swine fecal wastes and were 2.47 (95% confidence interval [CI] = 1.03, 5.94) and 2.30 times (95% CI = 0.90, 5.88) as prevalent proximal down- than proximal upstream of swine CAFOs, respectively. Pig-1-Bac and Pig-2-Bac were also 2.87 (95% CI = 1.21, 6.80) and 3.36 (95% CI = 1.34, 8.41) times as prevalent when 48 hour antecedent rainfall was greater than versus less than the mean, respectively. Results suggest diffuse and overall poor sanitary quality of surface waters where swine CAFO density is high. Pig-1-Bac and Pig-2-Bac are useful for tracking off-site conveyance of swine fecal wastes into surface waters proximal to and downstream of swine CAFOs and during rain events

Neurodegenerative disease risk among former international rugby union players

Background: Autopsy studies of former contact sports athletes, including soccer and rugby players, frequently report chronic traumatic encephalopathy, a neurodegenerative pathology associated with traumatic brain injury. Nevertheless, little is known about the risk of neurodegenerative disease in these populations. We hypothesised that neurodegenerative disease risk would be higher among former elite rugby union players than the general population. Methods: We conducted a retrospective cohort study accessing national electronic records on death certification, hospital admissions and dispensed prescriptions for a cohort of 412 male Scottish former international rugby union players and 1236 members of the general population, matched to former players by age, sex and area socioeconomic status. Mortality and incident neurodegenerative disease diagnoses among former rugby players were then compared with the matched comparison group. Results: Over a median 32 years follow-up from study entry at age 30 years, 121 (29.4%) former rugby players and 381 (30.8%) of the matched comparison group died. All-cause mortality was lower among former rugby players until 70 years of age with no difference thereafter. During follow-up, 47 (11.4%) former rugby players and 67 (5.4%) of the comparison group were diagnosed with incident neurodegenerative disease (HR 2.67, 95% CI 1.67 to 4.27, p<0.001). Conclusions: This study adds to our understanding of the association between contact sports participation and the risk of neurodegenerative disease. While further research exploring this interaction is required, in the meantime strategies to reduce exposure to head impacts and head injuries in sport should be promoted

Identifying sources of antibiotic resistance genes in the environment using the microbial Find, Inform, and Test framework

IntroductionAntimicrobial resistance (AMR) is an increasing public health concern for humans, animals, and the environment. However, the contributions of spatially distributed sources of AMR in the environment are not well defined.MethodsTo identify the sources of environmental AMR, the novel microbial Find, Inform, and Test (FIT) model was applied to a panel of five antibiotic resistance-associated genes (ARGs), namely, erm(B), tet(W), qnrA, sul1, and intI1, quantified from riverbed sediment and surface water from a mixed-use region.ResultsA one standard deviation increase in the modeled contributions of elevated AMR from bovine sources or land-applied waste sources [land application of biosolids, sludge, and industrial wastewater (i.e., food processing) and domestic (i.e., municipal and septage)] was associated with 34–80% and 33–77% increases in the relative abundances of the ARGs in riverbed sediment and surface water, respectively. Sources influenced environmental AMR at overland distances of up to 13 km.DiscussionOur study corroborates previous evidence of offsite migration of microbial pollution from bovine sources and newly suggests offsite migration from land-applied waste. With FIT, we estimated the distance-based influence range overland and downstream around sources to model the impact these sources may have on AMR at unsampled sites. This modeling supports targeted monitoring of AMR from sources for future exposure and risk mitigation efforts

Toward an integrative understanding of social behavior: new models and new opportunities.

Social interactions among conspecifics are a fundamental and adaptively significant component of the biology of numerous species. Such interactions give rise to group living as well as many of the complex forms of cooperation and conflict that occur within animal groups. Although previous conceptual models have focused on the ecological causes and fitness consequences of variation in social interactions, recent developments in endocrinology, neuroscience, and molecular genetics offer exciting opportunities to develop more integrated research programs that will facilitate new insights into the physiological causes and consequences of social variation. Here, we propose an integrative framework of social behavior that emphasizes relationships between ultimate-level function and proximate-level mechanism, thereby providing a foundation for exploring the full diversity of factors that underlie variation in social interactions, and ultimately sociality. In addition to identifying new model systems for the study of human psychopathologies, this framework provides a mechanistic basis for predicting how social behavior will change in response to environmental variation. We argue that the study of non-model organisms is essential for implementing this integrative model of social behavior because such species can be studied simultaneously in the lab and field, thereby allowing integration of rigorously controlled experimental manipulations with detailed observations of the ecological contexts in which interactions among conspecifics occur