scholarly journals Transient perturbation in neuro-ophthalmologic function after repetitive subconcussive head impacts: a randomized controlled trial

Neurology ◽  
2019 ◽  
Vol 93 (14 Supplement 1) ◽  
pp. S17.2-S17
Author(s):  
Keisuke Kawata ◽  
Madeleine Nowak ◽  
Zachary Bevilacqua ◽  
Keisuke Ejima ◽  
Megan Huibregtse ◽  
...  

ObjectiveTo examine the effect of subconcussive head impacts on neuro-ophthalmologic function tested by the King-Devick test (KDT).BackgroundSubconcussive head impacts can lead to insidious neurological impairment if sustained repetitively. The oculomotor system is sensitive to brain trauma; however, neuro-ophthalmologic response to subconcussive head impacts remain unclear.Design/MethodsSixty-eight healthy adult soccer players with at least 5 years of soccer heading experience were randomized into either a soccer heading group (n = 36) or soccer kicking-control group (n = 32). The independent variables were group (heading vs. kicking control) and assessment time points (pre-, 0 hr-, 2 hr-, and 24 hr-post-heading/kicking). At each time point, KDT performance was assessed. Between the pre and 0hr post time points, heading subjects then performed 10 soccer headers, with the ball traveled at 25 mph, over the course of 10 minutes. The control subjects kicked the soccer ball 10 times.ResultsThe heading group experienced a median linear head acceleration of 31.8g per head impact (IQR: 31.1–34.5g) and a median rotational head acceleration of 3.56 krad/sec2 per head impact (IQR: 2.93–4.04 krad/sec2). Conversely, soccer kicks did not result in a detectable level of head acceleration. The kicking control group showed a significant improvement in KDT performance over time, indicating the neuro-ophthalmologic adaptability and learning effect (pre, 42.5 ± 5.7 sec; 0 hr-post, 39.3 ± 5.9 sec; 2 h-post, 38.5 ± 5.8 sec; 24 h-post, 37.3 ± 6.1 sec). However, such improvement was blunted by repetitive soccer headings in the heading group (pre, 43.6 ± 7.8 sec; 0 hr-post, 42.7 ± 7.9 sec; 2 h-post, 42.6 ± 7.8 sec; 24 h-post, 40.7 ± 7.3 sec), as illustrated by significant time × group interactions at 0 hr (p = 0.012) and 2 hr (p = 0.002) post-heading/kicking time points in the mixed-effect regression model.ConclusionsOur data suggest that the neural circuit encompassing the brain and oculomotor system has tremendous abilities to adapt and improve its function if administered repeatedly, but subconcussive head impacts induced by soccer heading can transiently impair neuro-ophthalmologic function and its adaptive property.

2019 ◽  
Author(s):  
Megan Elizabeth Huibregtse ◽  
Keisuke Ejima ◽  
Zhongxue Chen ◽  
Zachary William Bevilacqua ◽  
Alekhya Koppineni ◽  
...  

Abstract Background: Chronic neuroinflammation has been implicated as a possible contributing mechanism in the development and progression of chronic traumatic encephalopathy. This neurodegenerative condition has been associated with longterm, repetitive exposure to subconcussive head impacts, defined as head impacts that do not induce clinical signs or symptoms of concussion. However, there is a gap in knowledge surrounding the acute inflammatory response to subconcussive head impacts. The present study aimed to test our hypothesis that plasma levels of two proinflammatory markers (CCL11, CCL2) and one anti-inflammatory marker (IL-10) would be significantly elevated after 10 repetitions of controlled subconcussive head impacts. Methods: This randomized controlled trial included 39 healthy adult soccer players who were randomized into a heading (n=22) or kicking-control group (n=17). The heading group executed 10 headers with soccer balls projected at a speed of 25mph. The kicking-control group followed the same protocol with 10 kicks. Plasma samples were collected pre-, 0h post-, 2h post-, and 24h post-intervention. Samples were assayed for CCL11, CCL2, and IL-10, which are inflammatory markers that have shown to upregulate following traumatic brain injury. The longitudinal inflammatory marker data were analyzed using mixed-effect regression models. Results: There were no significant group differences in the changes of plasma CCL11, CCL2, or IL-10 levels at post-intervention time points as compared with pre-intervention baseline. However, within the heading group, there was a statistically significant interaction between time and years of soccer heading experience in plasma CCL11 levels at 24h post-intervention (2.0 pg/mL per a single year of soccer heading experience, 95% CI: 0.8, 3.1, p = 0.001). Conclusions: Ten soccer headings did not modulate the acute response in the three inflammatory marker levels compared against a kicking-control group. However, the acute CCL11 response may be influenced by the duration of prior exposure to subconcussive head impacts. Our data provide a precedent for future field studies that prospectively track head impact exposure and the time course of changes in circulating CCL11.


2021 ◽  
Author(s):  
Yanyan Yang ◽  
Mazhong Zhang ◽  
Ying Sun ◽  
Zhezhe Peng ◽  
Xiaosu Zheng ◽  
...  

Abstract Background: Our aim was to investigate whether early surgical preparation by reading an animated picture book about procedure-related events could reduce the preoperative anxiety in preschoolers.Methods: 131 patients, aged 3-6 years and underwent elective minor surgery were randomized either to a control or a picture book group. Both groups received general information about surgery and anesthesia in pre-anesthesia clinic. Patients in study group also received a surgery-depicting picture book for them to read at home a week earlier before surgery. Child anxiety was evaluated with the modified Yale Preoperative Anxiety Scale Short Form in six observing time points before anesthesia induction, and the compliance of anesthesia induction was assessed with the Induction Compliance Checklist (ICC).Results: There were significantly lower anxiety scores in picture book group than in control group at the time of ready for intravenous cannulation in operation room [51.9 (23.6) vs. 67.2 (22.0); P = 0.001] and at the time of pre-anesthesia visit [27.8 (7.6) vs. 33.2 (13.6); P = 0.018]. No significant differences of anxiety levels were found between two groups at other observed time points: in the anesthesia outpatient clinic, in the holding area, at separation from parent to operating room (OR), and on entrance to OR (P = 0.584, 0.335, 0.228, 0.137, respectively). The percentage of children with poor induction compliance (i.e., ICC ≥ 6) was higher in control group compared with that in picture book group (38% vs.21%, P = 0.041).Conclusions: Home-reading an animated picture book to get familiar with the perioperative events earlier prior to surgery could effectively reduce the preoperative anxiety level and increase the compliance during the induction of anesthesia in preschool children.Trial registration: ChiCTR2000033583, 06/06/2020 www.chictr.org.cn.


2019 ◽  
Author(s):  
Aliza Werner-Seidler ◽  
Kit Huckvale ◽  
Mark E. Larsen ◽  
Alison L. Calear ◽  
Kate Maston ◽  
...  

Abstract Background Depression frequently first emerges during adolescence, and one in five young people will experience an episode of depression by the age of 18 years. Despite advances in treatment, there has been limited progress in addressing the burden at a population level. Accordingly, there has been growing interest in prevention approaches as an additional pathway to address depression. Depression can be prevented using evidence-based psychological programs. However, barriers to implementing and accessing these programs remain, typically reflecting a requirement for delivery by clinical experts and high associated delivery costs. Digital technologies, specifically smartphones, are now considered a key strategy to overcome the barriers inhibiting access to mental health programs. The Future Proofing Study is a large-scale school-based trial investigating whether Cognitive Behaviour Therapies (CBT) delivered by smartphone application can prevent depression.Methods A randomized controlled trial targeting up to 20,000 Year 8 Australian secondary school students will be conducted. In Stage I, schools will be randomized at the cluster level to receive either the CBT intervention app (SPARX) or to a non-active control group comparator. The primary outcome will be symptoms of depression and secondary outcomes include psychological distress, anxiety and insomnia. At the 12-month follow-up, participants in the intervention arm with elevated depressive symptoms will participate in an individual-level RCT (Stage II) and be randomised to receive a second CBT app which targets sleep difficulties (Sleep Ninja) or a control condition. Assessments will occur at post-intervention (both trial stages), and at 6, 12, 24, 36, 48- and 60-months post-baseline. Primary analyses will use an intention-to-treat approach and compare changes in symptoms from baseline to follow-up relative to the control group using mixed effect models.Discussion This is the first trial testing the effectiveness of smartphone apps delivered to school students to prevent depression at scale. Results from this trial will provide much needed insight into the feasibility of this approach. They stand to inform policy and commission decisions concerning if and how such programs should be deployed in school-based settings in Australia and beyond.


Author(s):  
Ernesto Cesar Pinto Leal-Junior ◽  
Marcelo Ferreira Duarte de Oliveira ◽  
Jon Joensen ◽  
Martin Bjørn Stausholm ◽  
Jan Magnus Bjordal ◽  
...  

Abstract Background The optimal time-response window for photobiomodulation therapy (PBMT) using low-level laser therapy (LLLT) and/or light emitting diodes therapy (LEDT) combined with static magnetic fields (sMF) before physical activity still was not fully investigated. The aim of the present study was to investigate the better of four time-response windows for PBMT combined with sMF (PBMT-sMF) use before exercise in humans. Methods A prospectively registered, randomized, triple-blinded (volunteers, therapists and assessors) placebo-controlled trial was carried out. Sixty healthy untrained male subjects were randomly allocated to six experimental groups (n = 10 per group): PBMT-sMF 5 mins, PBMT-sMF 3 h, PBMT-sMF 6 h, PBMT-sMF 1-day, placebo, and control. The control group performed all procedures, however did not receive any kind of intervention. PBMT-sMF active or PBMT-sMF placebo was applied precisely in different time points after baseline MVC test to ensure that both MVC tests and eccentric exercise protocol would occur at the same hour of the day in all groups. Then, after five minutes, 3 h, 6 h or 1-day (24 h) of PBMT-sMF treatment (active or placebo) the eccentric exercise protocol was performed. The primary outcome was peak torque obtained from maximum voluntary contraction (MVC). The secondary outcomes were creatine kinase (CK), and delayed onset muscle soreness (DOMS). The primary and secondary outcomes were measured at baseline, immediately after, 1 h, 24 h and 48 h after the eccentric exercise protocol. Results Sixty patients were randomized and analyzed to each sequence. The outcomes in absolute values show that all active PBMT-sMF groups increased (p < 0.05) MVC from immediately after to 1 h after eccentric exercise, and decreased (p < 0.05) CK activity at all time points. However, PBMT-sMF 5 mins, 3 h and 6 h groups showed better results in MVC and CK analysis from 24 h to 48 h, and also to DOMS (p < 0.05) at all time points. Participants did not report any adverse events. Conclusions PBMT-sMF can be used from 5 min to 6 h before exercise, and the effects can last up to 54 h after treatment. However, the effects start to decrease when a 1-day (24 h) time-response window is used. Trial registration NCT03420391. Registered 05 February 2018.


2014 ◽  
Vol 136 (9) ◽  
Author(s):  
Ray W. Daniel ◽  
Steven Rowson ◽  
Stefan M. Duma

The head impact exposure experienced by football players at the college and high school levels has been well documented; however, there are limited data regarding youth football despite its dramatically larger population. The objective of this study was to investigate head impact exposure in middle school football. Impacts were monitored using a commercially available accelerometer array installed inside the helmets of 17 players aged 12–14 years. A total of 4678 impacts were measured, with an average (±standard deviation) of 275 ± 190 impacts per player. The average of impact distributions for each player had a median impact of 22 ± 2 g and 954 ± 122 rad/s2, and a 95th percentile impact of 54 ± 9 g and 2525 ± 450 rad/s2. Similar to the head impact exposure experienced by high school and collegiate players, these data show that middle school football players experience a greater number of head impacts during games than practices. There were no significant differences between median and 95th percentile head acceleration magnitudes experienced during games and practices; however, a larger number of impacts greater than 80 g occurred during games than during practices. Impacts to the front and back of the helmet were most common. Overall, these data are similar to high school and college data that have been collected using similar methods. These data have applications toward youth football helmet design, the development of strategies designed to limit head impact exposure, and child-specific brain injury criteria.


BMJ Open ◽  
2020 ◽  
Vol 10 (10) ◽  
pp. e039343
Author(s):  
Thach Tran ◽  
Huong Thanh Nguyen ◽  
Ian Shochet ◽  
Astrid Wurfl ◽  
Jayne Orr ◽  
...  

IntroductionThe Resourceful Adolescent Program (RAP) is an evidence-based resilience intervention for adolescents. Operating in a strength-focused paradigm, the programme uses an integration of cognitive behavioural therapy and interpersonal psychotherapy to improve coping skills and build resilience. This study aims to establish whether a culturally and linguistically adapted intervention informed by RAP principles is effective in increasing resilience, enhancing coping skills and preventing symptoms of depression and anxiety.Methods and analysisWe will translate, back-translate and culturally adapt the RAP for adolescents and training materials for facilitators, and the adapted intervention will be called Happy House. A two-arm parallel controlled trial will be conducted in eight high schools in the north of Vietnam. In each of the selected schools, all students from four randomly selected grade 10 classes (an estimation of about 1204 students) will be invited to participate. The control group will receive the usual curriculum. The intervention group will receive six weekly 90 min school-based group sessions of Happy House in addition to the usual curriculum. The primary outcome, depressive symptoms, will be measured using a locally validated version of the Centre for Epidemiologic Studies Depression Scale Revised. Secondary outcomes are mental well-being, coping self-efficacy, school connectedness, anger management and health risk behaviours. Data will be collected at recruitment, and at two weeks and six months post intervention. Mixed-effect logistic regression for the main outcome and mixed-effect linear and logistic regression models for the secondary outcomes will be conducted to estimate the effects of the intervention on the outcomes.Ethics and disseminationThis trial has been approved by Monash University Human Research Ethics Committee (No. 21455) and the Institutional Review Board of the Hanoi School of Public Health (488/2019/YTCC-HD3). Dissemination of findings will include peer-reviewed publications, international and national conferences, seminar and media presentations, national policy briefings in Vietnam, local language reports and lay language summaries for participants.Trial registration numbersRegistered with the Australian New Zealand Clinical Trials Registry, registration number: ACTRN12620000088943 (3/2/2020).WHO Universal Trial Number: U1111-1246-4079.


Author(s):  
T. Reza Ferasyi ◽  
A. P. Koets ◽  
J. A. Stegeman ◽  
C. L.J.J. Kruitwagen

The present study was aimed to quantify the dynamics of early antigen specific proliferative responses of lymphocytes to (protein) antigens associated with experimentalMycobacterium avium subsp. paratuberculosis (Mp) infection cattle. The data were collected from20 experimentally infected calves, and 10 uninfected control animals, during the first 2 years oftheir lives. Several purified protein derivative antigens (Ppdp, Ppda, and Ppdb), tworecombinant Mp heatshock proteins (Hsp65 and Hsp70) and whole bacteria (sonicated Mpstrain 316F) were used to measure lymphocyte proliferation in a lymphocyte proliferationassay. Data were analyzed using a linear mixed effect (LME) model. The results showedsignificant group and timed effects for all antigens tested. At several time points, the responsesin the infected group were found significantly higher as compared to control group. The Ppdantigens induced similar lymphocyte proliferation patterns, as compared to whole bacteriaantigen and Hsp70. These results indicated that the antigen specific proliferative responses oflymphocytes differs for different antigens, probably related to differences in their availabilityduring different stages of infection. The application of LME model is a useful tool for analyzingthe quantitative longitudinal datasets. Keywords: dynamics, Mp, antigen, LME


2019 ◽  
Author(s):  
Aliza Werner-Seidler ◽  
Kit Huckvale ◽  
Mark E. Larsen ◽  
Alison L. Calear ◽  
Kate Maston ◽  
...  

Abstract Background Depression frequently first emerges during adolescence, and one in five young people will experience an episode of depression by the age of 18 years. Despite advances in treatment, there has been limited progress in addressing the burden at a population level. Accordingly, there has been growing interest in prevention approaches as an additional pathway to address depression. Depression can be prevented using evidence-based psychological programs. However, barriers to implementing and accessing these programs remain, typically reflecting a requirement for delivery by clinical experts and high associated delivery costs. Digital technologies, specifically smartphones, are now considered a key strategy to overcome the barriers inhibiting access to mental health programs. The Future Proofing Study is a large-scale school-based trial investigating whether Cognitive Behaviour Therapies (CBT) delivered by smartphone application can prevent depression.Methods A randomized controlled trial targeting up to 20,000 Year 8 Australian secondary school students will be conducted. In Stage I, schools will be randomized at the cluster level to receive either the CBT intervention app (SPARX) or to a non-active control group comparator. The primary outcome will be symptoms of depression and secondary outcomes include psychological distress, anxiety and insomnia. At the 12-month follow-up, participants in the intervention arm with elevated depressive symptoms will participate in an individual-level RCT (Stage II) and be randomised to receive a second CBT app which targets sleep difficulties (Sleep Ninja) or a control condition. Assessments will occur at post-intervention (both trial stages), and at 6, 12, 24, 36, 48- and 60-months post-baseline. Primary analyses will use an intention-to-treat approach and compare changes in symptoms from baseline to follow-up relative to the control group using mixed effect models.Discussion This is the first trial testing the effectiveness of smartphone apps delivered to school students to prevent depression at scale. Results from this trial will provide much needed insight into the feasibility of this approach. They stand to inform policy and commission decisions concerning if and how such programs should be deployed in school-based settings in Australia and beyond.


Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 874-874
Author(s):  
Karim Abou-Nassar ◽  
Marc Rodger ◽  
Michael J. Kovacs ◽  
Steve Doucette ◽  
Ramsay Tim ◽  
...  

Abstract Background: Low-molecular weight heparin (LMWH) is increasingly being used for prophylaxis of venous thromboembolism (VTE) and prevention of pregnancy associated morbidity in pregnant women with thrombophilia. Objective: We sought to determine if the administration of prophylactic doses of LMWH down regulates coagulation activation in high risk pregnant women with thrombophilia. Methods: This sub-study was planned as part of a randomized open label controlled trial (Thrombophilia in Pregnancy Prophylaxis Study (TIPPS)) in which patients at high risk of pregnancy complications with confirmed thrombophilia are randomized to receive either dalteparin (5000 units/day until 20 weeks then 5000U q12h until 37 weeks or onset of labor) or no treatment. Blood samples were collected at baseline, day 7–9 (after starting study drug), week 20 (before increasing study drug), week 36 (prior to stopping study drug) and at the time of admission to the labor and delivery unit. Samples were not drawn at fixed times in relation to drug injection. These samples were analyzed for levels of thrombin-antithrombin complexes (TAT), prothrombin fragments 1+2 (F1+2), D-dimer and anti-Xa activity. Generalized linear mixed models were used for statistical analysis and model results were controlled for age, smoking status, type of thrombophilia and predisposing risk factors. The effect of dalteparin on TAT levels was defined as the primary outcome. Results: Of one hundred ninety eight patients eligible, 114 were enrolled in TIPPS. Seventy four were eligible for the TIPPS coagulation activation sub-study and randomized. Twenty-three patients were analyzed in the treatment group (dalteparin) and 28 patients in the control group (no intervention). Levels of coagulation activation factors F1+2, TAT and D-dimer increased significantly throughout pregnancy in both groups (p&lt;0.0001). Dalteparin prophylaxis resulted in a significant increase in anti-Xa activity through pregnancy (p&lt;0.0001) compared to controls. Dalteparin had no significant effects on the levels of TAT, F1+2 and D-dimer throughout pregnancy in thrombophilic women (figure 1). A post hoc Monte Carlo power analysis revealed that our study had over 99% and 64% power to detect reductions in TAT values on treatment of respectively 50% and 25%. Conclusion: Prophylaxis with dalteparin at doses used in this study did not reduce coagulation activation in high risk thrombophilic women during pregnancy. Figure 1 Box plots of TAT levels in high risk pregnant thrombophilic women with (closed boxes) and without (open boxes) dalteparin thromboprophylaxis at different time points during pregnancy. Day 7 represents the time after radomization in TIPPS whereas at other time points represent sepcific gestational ages. The bottom of the boxes mark the 25th percentile, the median lines mark the 50th percentile, the top of the boxes mark the 75th percentile, the bottom and top of the vertical lines mark the 5th and 95th percentile, respectively. Figure 1. Box plots of TAT levels in high risk pregnant thrombophilic women with (closed boxes) and without (open boxes) dalteparin thromboprophylaxis at different time points during pregnancy. Day 7 represents the time after radomization in TIPPS whereas at other time points represent sepcific gestational ages. The bottom of the boxes mark the 25th percentile, the median lines mark the 50th percentile, the top of the boxes mark the 75th percentile, the bottom and top of the vertical lines mark the 5th and 95th percentile, respectively.


2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Jonathan De Fallois ◽  
Lorenz Weidhase ◽  
Sirak Petros

Abstract Background and Aims Acute kidney injury (AKI) is frequent among critically ill patients and it is associated with high mortality. Rhabdomyolysis is a distinct cause of AKI. As myoglobin has renal toxic effects, clearance via continuous renal replacement therapy (CRRT) may be favourable. Current international guidelines recommend regional citrate anticoagulation (RCA). Clinical data comparing different modalities of CRRT addressing myoglobin clearance are lacking. Hemofiltration is recommended to eliminate myoglobin, which requires systemic anticoagulation. RCA would be impractical due to the high citrate load as a result of the higher blood flow. Continuous veno-venous hemodiafiltration (CVVHDF) is one opportunity to realize lower citrate load and maintain middle molecule clearance. Another approach may be the application of hemodialysis with high cut-off (HCO) membranes with a pore size larger than 0.01 μm in CVVHD (CVVHD-HCO). We have previously shown that CVVHD-HCO is superior to conventional high-flux dialyser regarding the clearance of β2-microglobulin. Based on this finding, we analyzed of various etiologiesre Filter lilifespan mit dem efonnummer der Virologie zum Befunderfragenmyoglobin clearance with CVVHDF compared to CVVHD-HCO with RCA. Method The present study is a prospective, randomized, single-blinded, monocentric trial. We enrolled patients from May 2017 to September 2018 in our 28-bed medical ICU at the University Hospital Leipzig. We screened 430 patients with AKI and indication for RRT for eligibility. A total of 70 patients underwent randomisation 1:1 into the intervention (CVVHD-HCO, high cut-off dialyzer Ultraflux EMiC2) and control group (CVVHDF, high-flux dialyzer Ultraflux AV1000S). The concentrations of myoglobin (17053 Dalton (Da), urea (60 Da), creatinine (113 Da), β2-microglobulin 11800 Da), interleukin 6 (IL-6, 26000 Da) and albumin (66470 Da) were measured before (pre) and after (post) the dialyzer 1, 6, 12, 24 and 48 h after initiating CRRT. We hypothesized non-inferiority of CVVHD-HCO versus CVVHDF regarding myoglobin clearance (primary end-point). Results Myoglobin clearance showed non-inferiority in the intervention group for all time points. The dialyzer in the intervention group resulted in even a better myoglobin clearance during the whole study period. (Table 1). Clearance values for urea and creatinine were equal and there was no albumin loss in both groups.β2-microglobulin clearance was significantly better in the intervention group than in the control group at all time points. The clearance of IL-6 was also better at T0 in the intervention group. The filter lifespan was 51.5 hours (CI: 44.24; 58.76) in the control group and 62.3 hours (CI 56.83; 67.7) in the intervention group (log-rank, p=0,029). Conclusion Myoglobin can be reliably cleared using both CVVHD-HCO and CVVHDF. Nevertheless, the plasma specific clearance rate of myoglobin was higher with CVVHD-HCO. High myoglobin levels are associated with AKI and higher mortality rates and on this account clearance of myoglobin represents a relevant clinical issue.


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