How Much Rugby is Too Much? A Seven-Season Prospective Cohort Study of Match Exposure and Injury Risk in Professional Rugby Union Players.

INTRODUCTION: Numerous studies have documented the incidence and nature of injuries in professional rugby union, but few have identified specific risk factors for injury in this population using appropriate statistical methods. In particular, little is known about the role of previous short-term or longer-term match exposures in current injury risk in this setting. OBJECTIVES: Our objective was to investigate the influence that match exposure has upon injury risk in rugby union. METHOD: We conducted a seven-season (2006/7-2012/13) prospective cohort study of time-loss injuries in 1253 English premiership professional players. Players' 12-month match exposure (number of matches a player was involved in for ≥20 min in the preceding 12 months) and 1-month match exposure (number of full-game equivalent [FGE] matches in preceding 30 days) were assessed as risk factors for injury using a nested frailty model and magnitude-based inferences. RESULTS: The 12-month match exposure was associated with injury risk in a non-linear fashion; players who had been involved in fewer than ≈15 or more than ≈35 matches over the preceding 12-month period were more susceptible to injury. Monthly match exposure was linearly associated with injury risk (hazard ratio [HR]: 1.14 per 2 standard deviation [3.2 FGE] increase, 90% confidence interval [CI] 1.08-1.20; likely harmful), although this effect was substantially attenuated for players in the upper quartile for 12-month match exposures (>28 matches). CONCLUSION: A player's accumulated (12-month) and recent (1-month) match exposure substantially influences their current injury risk. Careful attention should be paid to planning the workloads and monitoring the responses of players involved in: (1) a high (>≈35) number of matches in the previous year, (2) a low (<≈15) number of matches in the previous year, and (3) a low-moderate number of matches in previous year but who have played intensively in the recent past. These findings make a major contribution to evidence-based policy decisions regarding match workload limits in professional rugby union

Mortality and pulmonary complications in patients undergoing surgery with perioperative SARS-CoV-2 infection: an international cohort study

Background: The impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on postoperative recovery needs to be understood to inform clinical decision making during and after the COVID-19 pandemic. This study reports 30-day mortality and pulmonary complication rates in patients with perioperative SARS-CoV-2 infection. Methods: This international, multicentre, cohort study at 235 hospitals in 24 countries included all patients undergoing surgery who had SARS-CoV-2 infection confirmed within 7 days before or 30 days after surgery. The primary outcome measure was 30-day postoperative mortality and was assessed in all enrolled patients. The main secondary outcome measure was pulmonary complications, defined as pneumonia, acute respiratory distress syndrome, or unexpected postoperative ventilation. Findings: This analysis includes 1128 patients who had surgery between Jan 1 and March 31, 2020, of whom 835 (74·0%) had emergency surgery and 280 (24·8%) had elective surgery. SARS-CoV-2 infection was confirmed preoperatively in 294 (26·1%) patients. 30-day mortality was 23·8% (268 of 1128). Pulmonary complications occurred in 577 (51·2%) of 1128 patients; 30-day mortality in these patients was 38·0% (219 of 577), accounting for 81·7% (219 of 268) of all deaths. In adjusted analyses, 30-day mortality was associated with male sex (odds ratio 1·75 [95% CI 1·28–2·40], p\textless0·0001), age 70 years or older versus younger than 70 years (2·30 [1·65–3·22], p\textless0·0001), American Society of Anesthesiologists grades 3–5 versus grades 1–2 (2·35 [1·57–3·53], p\textless0·0001), malignant versus benign or obstetric diagnosis (1·55 [1·01–2·39], p=0·046), emergency versus elective surgery (1·67 [1·06–2·63], p=0·026), and major versus minor surgery (1·52 [1·01–2·31], p=0·047). Interpretation: Postoperative pulmonary complications occur in half of patients with perioperative SARS-CoV-2 infection and are associated with high mortality. Thresholds for surgery during the COVID-19 pandemic should be higher than during normal practice, particularly in men aged 70 years and older. Consideration should be given for postponing non-urgent procedures and promoting non-operative treatment to delay or avoid the need for surgery. Funding: National Institute for Health Research (NIHR), Association of Coloproctology of Great Britain and Ireland, Bowel and Cancer Research, Bowel Disease Research Foundation, Association of Upper Gastrointestinal Surgeons, British Association of Surgical Oncology, British Gynaecological Cancer Society, European Society of Coloproctology, NIHR Academy, Sarcoma UK, Vascular Society for Great Britain and Ireland, and Yorkshire Cancer Research

Analysis of the effects of a novel anti-inflammatory on anxiety, apathy, and cognition in a mouse model of Alzheimer’s Disease

Alzheimer’s Disease (AD) is the most common form of dementia. It is a fatal neurodegenerative disease that leads to both cognitive decline and altered psychological states. There is currently no cure for AD. The pathology of AD includes the clustering of insoluble amyloid-β (Aβ) plaques, tau tangles, and increased neuroinflammation. These pathological manifestations initially occur in the hippocampus (HPC), then continue to the prefrontal cortex (PFC), and occur throughout the brain as the disease progresses. The heightened neuroinflammatory state in AD is an essential point of focus in AD research. In this study, the novel oral anti-inflammatory tumor necrosis factor-α (TNF-α) inhibitor compound PD2244 was tested to observe its effects on sensorimotor gating using prepulse inhibition (PPI), spatial memory using Barnes Maze, anxiety using an elevated-T maze, and apathy by observing nest building behavior in both female and male 3xTg mice. The 3xTg mice are the only triple-transgenic models of AD that have both Aβ plaques and tau tangles and is also an accelerated mouse model of AD pathology onset. A specialized diet containing variable doses of PD2244 was given to 3xTg mice beginning at 6 months of age. The doses given were 0, 1, 3, 10, and 30 mg/kg of PD2244. Testing was then performed at 9, 12, and 15 months, where 15 months equated to thorough AD pathology. Regarding behavioral improvement, it was observed that all doses of PD2244 were effective to alleviate deficits in PPI at 9, 12, and 15 months of age. On the Barnes Maze, at 9 months of age the 10 mg/kg dose of PD2244 was effective to alleviate deficits, whereas at 12 months of age, 3 and 30 mg/kg dose of PD2244 was effective, and finally, at 15 months of age the 3, 10 and 30 mg/kg doses of PD2244 demonstrated efficacy to alleviate deficits in spatial memory performance. On the elevated T-maze, there were no effects at 9 months of age, but the 3 mg/kg dose of PD2244 resulted in anxiolytic effects at 12 and 15 months of age. Nest building behavior is also being observed in 15-month-old mice to determine effects of PD2244 on apathy since it is a common neuropsychiatric prodrome of AD. Finally, analysis of neurobiological markers has revealed that PD2244 reduced increases in the proinflammatory cytokines TNF-α and interkeukin-1β (IL-1β) at 15 months of age in the HPC. In addition, there is currently a project analyzing immunohistological staining of microglial cells in the HPC and PFC in 15-month-old animals. This project is designed to discover a novel, effective, anti-inflammatory treatment for cognitive deficits and increases in anxiety associate with AD